NO163453B - PROCEDURE FOR THE PREPARATION OF SPHINGOSIN DERIVATIVES. - Google Patents
PROCEDURE FOR THE PREPARATION OF SPHINGOSIN DERIVATIVES. Download PDFInfo
- Publication number
- NO163453B NO163453B NO863251A NO863251A NO163453B NO 163453 B NO163453 B NO 163453B NO 863251 A NO863251 A NO 863251A NO 863251 A NO863251 A NO 863251A NO 163453 B NO163453 B NO 163453B
- Authority
- NO
- Norway
- Prior art keywords
- compound
- formula
- group
- azido
- acid
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims abstract description 36
- 238000002360 preparation method Methods 0.000 title claims abstract description 7
- WWUZIQQURGPMPG-KRWOKUGFSA-N sphingosine Chemical class CCCCCCCCCCCCC\C=C\[C@@H](O)[C@@H](N)CO WWUZIQQURGPMPG-KRWOKUGFSA-N 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 96
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 29
- 125000002252 acyl group Chemical group 0.000 claims abstract description 21
- 125000006239 protecting group Chemical group 0.000 claims abstract description 20
- WQZGKKKJIJFFOK-SVZMEOIVSA-N (+)-Galactose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-SVZMEOIVSA-N 0.000 claims abstract description 18
- -1 amino compound Chemical class 0.000 claims abstract description 17
- 150000003410 sphingosines Chemical class 0.000 claims abstract description 12
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims abstract description 10
- 125000001931 aliphatic group Chemical group 0.000 claims abstract description 8
- 235000014113 dietary fatty acids Nutrition 0.000 claims abstract description 8
- 239000000194 fatty acid Substances 0.000 claims abstract description 8
- 229930195729 fatty acid Natural products 0.000 claims abstract description 8
- 150000004665 fatty acids Chemical class 0.000 claims abstract description 8
- YTBSYETUWUMLBZ-QWWZWVQMSA-N D-threose Chemical compound OC[C@@H](O)[C@H](O)C=O YTBSYETUWUMLBZ-QWWZWVQMSA-N 0.000 claims abstract description 6
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 53
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 24
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 22
- 239000000203 mixture Substances 0.000 claims description 20
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 15
- 238000006243 chemical reaction Methods 0.000 claims description 15
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 11
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 claims description 9
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 9
- 239000002253 acid Substances 0.000 claims description 8
- 239000002585 base Substances 0.000 claims description 8
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical group O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 claims description 8
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 7
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 7
- RWSOTUBLDIXVET-UHFFFAOYSA-N Dihydrogen sulfide Chemical compound S RWSOTUBLDIXVET-UHFFFAOYSA-N 0.000 claims description 6
- 150000003839 salts Chemical class 0.000 claims description 6
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims description 5
- 230000006181 N-acylation Effects 0.000 claims description 5
- 125000003118 aryl group Chemical group 0.000 claims description 5
- 125000004432 carbon atom Chemical group C* 0.000 claims description 5
- 239000003795 chemical substances by application Substances 0.000 claims description 5
- 150000007530 organic bases Chemical group 0.000 claims description 5
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 claims description 5
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 claims description 4
- 239000005711 Benzoic acid Substances 0.000 claims description 4
- 229910052783 alkali metal Inorganic materials 0.000 claims description 4
- 235000010233 benzoic acid Nutrition 0.000 claims description 4
- 150000004820 halides Chemical class 0.000 claims description 4
- FDPIMTJIUBPUKL-UHFFFAOYSA-N pentan-3-one Chemical compound CCC(=O)CC FDPIMTJIUBPUKL-UHFFFAOYSA-N 0.000 claims description 4
- NHKJPPKXDNZFBJ-UHFFFAOYSA-N phenyllithium Chemical compound [Li]C1=CC=CC=C1 NHKJPPKXDNZFBJ-UHFFFAOYSA-N 0.000 claims description 4
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Substances [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 4
- 239000004215 Carbon black (E152) Substances 0.000 claims description 3
- 238000005903 acid hydrolysis reaction Methods 0.000 claims description 3
- 230000004913 activation Effects 0.000 claims description 3
- 150000001299 aldehydes Chemical class 0.000 claims description 3
- RXKJFZQQPQGTFL-UHFFFAOYSA-N dihydroxyacetone Chemical compound OCC(=O)CO RXKJFZQQPQGTFL-UHFFFAOYSA-N 0.000 claims description 3
- 229910001385 heavy metal Inorganic materials 0.000 claims description 3
- 229930195733 hydrocarbon Natural products 0.000 claims description 3
- 150000002430 hydrocarbons Chemical class 0.000 claims description 3
- 239000007800 oxidant agent Substances 0.000 claims description 3
- 230000003647 oxidation Effects 0.000 claims description 3
- 238000007254 oxidation reaction Methods 0.000 claims description 3
- UTQNKKSJPHTPBS-UHFFFAOYSA-N 2,2,2-trichloroethanone Chemical group ClC(Cl)(Cl)[C]=O UTQNKKSJPHTPBS-UHFFFAOYSA-N 0.000 claims description 2
- 150000007933 aliphatic carboxylic acids Chemical class 0.000 claims description 2
- 125000000217 alkyl group Chemical group 0.000 claims description 2
- 150000003934 aromatic aldehydes Chemical class 0.000 claims description 2
- HUMNYLRZRPPJDN-KWCOIAHCSA-N benzaldehyde Chemical group O=[11CH]C1=CC=CC=C1 HUMNYLRZRPPJDN-KWCOIAHCSA-N 0.000 claims description 2
- 150000001558 benzoic acid derivatives Chemical class 0.000 claims description 2
- 239000011230 binding agent Substances 0.000 claims description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- 239000003638 chemical reducing agent Substances 0.000 claims description 2
- 150000002009 diols Chemical class 0.000 claims description 2
- 150000002148 esters Chemical class 0.000 claims description 2
- 150000008282 halocarbons Chemical class 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- 150000007529 inorganic bases Chemical class 0.000 claims description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
- IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical class CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 claims description 2
- ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 claims description 2
- 239000012279 sodium borohydride Substances 0.000 claims description 2
- 229910000033 sodium borohydride Inorganic materials 0.000 claims description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 2
- 238000005858 glycosidation reaction Methods 0.000 claims 1
- 230000036571 hydration Effects 0.000 claims 1
- 238000006703 hydration reaction Methods 0.000 claims 1
- 150000002576 ketones Chemical class 0.000 claims 1
- ACKFDYCQCBEDNU-UHFFFAOYSA-J lead(2+);tetraacetate Chemical compound [Pb+2].CC([O-])=O.CC([O-])=O.CC([O-])=O.CC([O-])=O ACKFDYCQCBEDNU-UHFFFAOYSA-J 0.000 claims 1
- 239000011968 lewis acid catalyst Substances 0.000 claims 1
- 239000012299 nitrogen atmosphere Substances 0.000 claims 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 claims 1
- 238000000926 separation method Methods 0.000 abstract description 6
- 238000007239 Wittig reaction Methods 0.000 abstract description 2
- 125000003277 amino group Chemical group 0.000 abstract 1
- 230000001590 oxidative effect Effects 0.000 abstract 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 87
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 72
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 42
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 42
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 33
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 28
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 22
- 239000000741 silica gel Substances 0.000 description 21
- 229910002027 silica gel Inorganic materials 0.000 description 21
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 18
- 239000003208 petroleum Substances 0.000 description 17
- 238000000746 purification Methods 0.000 description 17
- 235000019439 ethyl acetate Nutrition 0.000 description 14
- 229910052757 nitrogen Inorganic materials 0.000 description 14
- 238000005160 1H NMR spectroscopy Methods 0.000 description 13
- 239000012074 organic phase Substances 0.000 description 12
- 239000000243 solution Substances 0.000 description 12
- KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 description 10
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 9
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 9
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 8
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 7
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 7
- 230000015572 biosynthetic process Effects 0.000 description 7
- 238000003786 synthesis reaction Methods 0.000 description 7
- WGXOIVORNNWRAD-UHFFFAOYSA-N 5-hydroxy-2-phenyl-1,3-dioxane-4-carbaldehyde Chemical compound O1C(C=O)C(O)COC1C1=CC=CC=C1 WGXOIVORNNWRAD-UHFFFAOYSA-N 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- 229920006395 saturated elastomer Polymers 0.000 description 6
- 239000008346 aqueous phase Substances 0.000 description 5
- 229940106189 ceramide Drugs 0.000 description 5
- 238000004519 manufacturing process Methods 0.000 description 5
- CCCMONHAUSKTEQ-UHFFFAOYSA-N octadecene Natural products CCCCCCCCCCCCCCCCC=C CCCMONHAUSKTEQ-UHFFFAOYSA-N 0.000 description 5
- 229910052938 sodium sulfate Inorganic materials 0.000 description 5
- 235000011152 sodium sulphate Nutrition 0.000 description 5
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 4
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 4
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 4
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 4
- WTEOIRVLGSZEPR-UHFFFAOYSA-N boron trifluoride Chemical compound FB(F)F WTEOIRVLGSZEPR-UHFFFAOYSA-N 0.000 description 4
- QARVLSVVCXYDNA-UHFFFAOYSA-N bromobenzene Chemical compound BrC1=CC=CC=C1 QARVLSVVCXYDNA-UHFFFAOYSA-N 0.000 description 4
- 150000002500 ions Chemical class 0.000 description 4
- 229910052744 lithium Inorganic materials 0.000 description 4
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 4
- 235000019341 magnesium sulphate Nutrition 0.000 description 4
- 238000002844 melting Methods 0.000 description 4
- 230000008018 melting Effects 0.000 description 4
- 239000003960 organic solvent Substances 0.000 description 4
- JQWHASGSAFIOCM-UHFFFAOYSA-M sodium periodate Chemical compound [Na+].[O-]I(=O)(=O)=O JQWHASGSAFIOCM-UHFFFAOYSA-M 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- YDNKGFDKKRUKPY-JHOUSYSJSA-N C16 ceramide Natural products CCCCCCCCCCCCCCCC(=O)N[C@@H](CO)[C@H](O)C=CCCCCCCCCCCCCC YDNKGFDKKRUKPY-JHOUSYSJSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- CRJGESKKUOMBCT-VQTJNVASSA-N N-acetylsphinganine Chemical compound CCCCCCCCCCCCCCC[C@@H](O)[C@H](CO)NC(C)=O CRJGESKKUOMBCT-VQTJNVASSA-N 0.000 description 3
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 206010052428 Wound Diseases 0.000 description 3
- 208000027418 Wounds and injury Diseases 0.000 description 3
- ZVEQCJWYRWKARO-UHFFFAOYSA-N ceramide Natural products CCCCCCCCCCCCCCC(O)C(=O)NC(CO)C(O)C=CCCC=C(C)CCCCCCCCC ZVEQCJWYRWKARO-UHFFFAOYSA-N 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- VVGIYYKRAMHVLU-UHFFFAOYSA-N newbouldiamide Natural products CCCCCCCCCCCCCCCCCCCC(O)C(O)C(O)C(CO)NC(=O)CCCCCCCCCCCCCCCCC VVGIYYKRAMHVLU-UHFFFAOYSA-N 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 239000001632 sodium acetate Substances 0.000 description 3
- 235000017281 sodium acetate Nutrition 0.000 description 3
- 235000017557 sodium bicarbonate Nutrition 0.000 description 3
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- WJKHJLXJJJATHN-UHFFFAOYSA-N triflic anhydride Chemical compound FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F WJKHJLXJJJATHN-UHFFFAOYSA-N 0.000 description 3
- MEKOFIRRDATTAG-UHFFFAOYSA-N 2,2,5,8-tetramethyl-3,4-dihydrochromen-6-ol Chemical compound C1CC(C)(C)OC2=C1C(C)=C(O)C=C2C MEKOFIRRDATTAG-UHFFFAOYSA-N 0.000 description 2
- YQTCQNIPQMJNTI-UHFFFAOYSA-N 2,2-dimethylpropan-1-one Chemical group CC(C)(C)[C]=O YQTCQNIPQMJNTI-UHFFFAOYSA-N 0.000 description 2
- OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 2
- 229910015900 BF3 Inorganic materials 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 2
- 150000000780 D-glucose derivatives Chemical class 0.000 description 2
- ULGZDMOVFRHVEP-RWJQBGPGSA-N Erythromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 ULGZDMOVFRHVEP-RWJQBGPGSA-N 0.000 description 2
- XPDWGBQVDMORPB-UHFFFAOYSA-N Fluoroform Chemical class FC(F)F XPDWGBQVDMORPB-UHFFFAOYSA-N 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- 239000002841 Lewis acid Substances 0.000 description 2
- JLTDJTHDQAWBAV-UHFFFAOYSA-N N,N-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 2
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 150000001783 ceramides Chemical class 0.000 description 2
- GWHCXVQVJPWHRF-UHFFFAOYSA-N cis-tetracosenoic acid Natural products CCCCCCCCC=CCCCCCCCCCCCCCC(O)=O GWHCXVQVJPWHRF-UHFFFAOYSA-N 0.000 description 2
- 230000032050 esterification Effects 0.000 description 2
- 238000005886 esterification reaction Methods 0.000 description 2
- IPCSVZSSVZVIGE-UHFFFAOYSA-N hexadecanoic acid Chemical compound CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 2
- ARBOVOVUTSQWSS-UHFFFAOYSA-N hexadecanoyl chloride Chemical compound CCCCCCCCCCCCCCCC(Cl)=O ARBOVOVUTSQWSS-UHFFFAOYSA-N 0.000 description 2
- 239000011261 inert gas Substances 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- 150000007517 lewis acids Chemical class 0.000 description 2
- AMXOYNBUYSYVKV-UHFFFAOYSA-M lithium bromide Chemical compound [Li+].[Br-] AMXOYNBUYSYVKV-UHFFFAOYSA-M 0.000 description 2
- 125000004170 methylsulfonyl group Chemical class [H]C([H])([H])S(*)(=O)=O 0.000 description 2
- 239000002808 molecular sieve Substances 0.000 description 2
- VAMFXQBUQXONLZ-UHFFFAOYSA-N n-alpha-eicosene Natural products CCCCCCCCCCCCCCCCCCC=C VAMFXQBUQXONLZ-UHFFFAOYSA-N 0.000 description 2
- IOLCXVTUBQKXJR-UHFFFAOYSA-M potassium bromide Chemical compound [K+].[Br-] IOLCXVTUBQKXJR-UHFFFAOYSA-M 0.000 description 2
- 229960001153 serine Drugs 0.000 description 2
- NDVLTYZPCACLMA-UHFFFAOYSA-N silver oxide Chemical compound [O-2].[Ag+].[Ag+] NDVLTYZPCACLMA-UHFFFAOYSA-N 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- BDHFUVZGWQCTTF-UHFFFAOYSA-N sulfonic acid Chemical compound OS(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-N 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 238000004809 thin layer chromatography Methods 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- JBWKIWSBJXDJDT-UHFFFAOYSA-N triphenylmethyl chloride Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(Cl)C1=CC=CC=C1 JBWKIWSBJXDJDT-UHFFFAOYSA-N 0.000 description 2
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 2
- WWUZIQQURGPMPG-UHFFFAOYSA-N (-)-D-erythro-Sphingosine Natural products CCCCCCCCCCCCCC=CC(O)C(N)CO WWUZIQQURGPMPG-UHFFFAOYSA-N 0.000 description 1
- GWHCXVQVJPWHRF-KTKRTIGZSA-N (15Z)-tetracosenoic acid Chemical compound CCCCCCCC\C=C/CCCCCCCCCCCCCC(O)=O GWHCXVQVJPWHRF-KTKRTIGZSA-N 0.000 description 1
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
- ULNRTPCFRBIMKL-GHVJWSGMSA-N (e)-2-tetracosenoic acid Chemical compound CCCCCCCCCCCCCCCCCCCCC\C=C\C(O)=O ULNRTPCFRBIMKL-GHVJWSGMSA-N 0.000 description 1
- ZXSQEZNORDWBGZ-UHFFFAOYSA-N 1,3-dihydropyrrolo[2,3-b]pyridin-2-one Chemical compound C1=CN=C2NC(=O)CC2=C1 ZXSQEZNORDWBGZ-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- TWJNQYPJQDRXPH-UHFFFAOYSA-N 2-cyanobenzohydrazide Chemical compound NNC(=O)C1=CC=CC=C1C#N TWJNQYPJQDRXPH-UHFFFAOYSA-N 0.000 description 1
- UFOOFOUFKSIFCD-KTKRTIGZSA-N 2-hydroxynervonic acid Chemical compound CCCCCCCC\C=C/CCCCCCCCCCCCC(O)C(O)=O UFOOFOUFKSIFCD-KTKRTIGZSA-N 0.000 description 1
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
- RTKMFQOHBDVEBC-UHFFFAOYSA-N 3-bromo-3-buten-1-ol Chemical compound OCCC(Br)=C RTKMFQOHBDVEBC-UHFFFAOYSA-N 0.000 description 1
- JDTMOBCXZZCLPF-UHFFFAOYSA-N 4,6-O-Isopropylidene-D-Galactose Natural products CC1COCC2OC(O)C(O)C(O)C2O1 JDTMOBCXZZCLPF-UHFFFAOYSA-N 0.000 description 1
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 1
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
- 101150041968 CDC13 gene Proteins 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 208000032544 Cicatrix Diseases 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 229910021578 Iron(III) chloride Inorganic materials 0.000 description 1
- 235000021353 Lignoceric acid Nutrition 0.000 description 1
- CQXMAMUUWHYSIY-UHFFFAOYSA-N Lignoceric acid Natural products CCCCCCCCCCCCCCCCCCCCCCCC(=O)OCCC1=CC=C(O)C=C1 CQXMAMUUWHYSIY-UHFFFAOYSA-N 0.000 description 1
- OYHQOLUKZRVURQ-HZJYTTRNSA-N Linoleic acid Chemical compound CCCCC\C=C/C\C=C/CCCCCCCC(O)=O OYHQOLUKZRVURQ-HZJYTTRNSA-N 0.000 description 1
- 235000021360 Myristic acid Nutrition 0.000 description 1
- TUNFSRHWOTWDNC-UHFFFAOYSA-N Myristic acid Natural products CCCCCCCCCCCCCC(O)=O TUNFSRHWOTWDNC-UHFFFAOYSA-N 0.000 description 1
- XJXROGWVRIJYMO-SJDLZYGOSA-N Nervonic acid Natural products O=C(O)[C@@H](/C=C/CCCCCCCC)CCCCCCCCCCCC XJXROGWVRIJYMO-SJDLZYGOSA-N 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- 239000005642 Oleic acid Substances 0.000 description 1
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 1
- 235000021314 Palmitic acid Nutrition 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 208000025865 Ulcer Diseases 0.000 description 1
- FOBZYNWKGHDEII-SFFUCWETSA-N [(2R,3R,4S,5R,6S)-3,4,5-tris(2,2-dimethylpropanoyloxy)-6-[(2,2,2-trichloroacetyl)amino]oxan-2-yl]methyl 2,2-dimethylpropanoate Chemical compound CC(C)(C)C(=O)OC[C@H]1O[C@H](NC(=O)C(Cl)(Cl)Cl)[C@H](OC(=O)C(C)(C)C)[C@@H](OC(=O)C(C)(C)C)[C@@H]1OC(=O)C(C)(C)C FOBZYNWKGHDEII-SFFUCWETSA-N 0.000 description 1
- FANSUBKOMODXIC-CBQIKETKSA-N [(2r,3r,4s,5s,6r)-2-chloro-4,5-dihydroxy-6-(hydroxymethyl)oxan-3-yl] acetate Chemical compound CC(=O)O[C@H]1[C@@H](Cl)O[C@H](CO)[C@@H](O)[C@@H]1O FANSUBKOMODXIC-CBQIKETKSA-N 0.000 description 1
- NZHXEWZGTQSYJM-UHFFFAOYSA-N [bromo(diphenyl)methyl]benzene Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(Br)C1=CC=CC=C1 NZHXEWZGTQSYJM-UHFFFAOYSA-N 0.000 description 1
- PNZVFASWDSMJER-UHFFFAOYSA-N acetic acid;lead Chemical compound [Pb].CC(O)=O PNZVFASWDSMJER-UHFFFAOYSA-N 0.000 description 1
- 150000008065 acid anhydrides Chemical class 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 238000007259 addition reaction Methods 0.000 description 1
- HOPRXXXSABQWAV-UHFFFAOYSA-N anhydrous collidine Natural products CC1=CC=NC(C)=C1C HOPRXXXSABQWAV-UHFFFAOYSA-N 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- MSUOLNSQHLHDAS-UHFFFAOYSA-N cerebronic acid Chemical compound CCCCCCCCCCCCCCCCCCCCCCC(O)C(O)=O MSUOLNSQHLHDAS-UHFFFAOYSA-N 0.000 description 1
- 229920001429 chelating resin Polymers 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- UTBIMNXEDGNJFE-UHFFFAOYSA-N collidine Natural products CC1=CC=C(C)C(C)=N1 UTBIMNXEDGNJFE-UHFFFAOYSA-N 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- HPYNZHMRTTWQTB-UHFFFAOYSA-N dimethylpyridine Natural products CC1=CC=CN=C1C HPYNZHMRTTWQTB-UHFFFAOYSA-N 0.000 description 1
- 238000006073 displacement reaction Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- UXMZNEHSMYESLH-UHFFFAOYSA-M hexadecyl(triphenyl)phosphanium;bromide Chemical compound [Br-].C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(CCCCCCCCCCCCCCCC)C1=CC=CC=C1 UXMZNEHSMYESLH-UHFFFAOYSA-M 0.000 description 1
- 229910000037 hydrogen sulfide Inorganic materials 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
- 235000020778 linoleic acid Nutrition 0.000 description 1
- OYHQOLUKZRVURQ-IXWMQOLASA-N linoleic acid Natural products CCCCC\C=C/C\C=C\CCCCCCCC(O)=O OYHQOLUKZRVURQ-IXWMQOLASA-N 0.000 description 1
- 150000002642 lithium compounds Chemical class 0.000 description 1
- JILPJDVXYVTZDQ-UHFFFAOYSA-N lithium methoxide Chemical compound [Li+].[O-]C JILPJDVXYVTZDQ-UHFFFAOYSA-N 0.000 description 1
- 229940075610 mercuric cyanide Drugs 0.000 description 1
- 150000002736 metal compounds Chemical class 0.000 description 1
- IZDROVVXIHRYMH-UHFFFAOYSA-N methanesulfonic anhydride Chemical compound CS(=O)(=O)OS(C)(=O)=O IZDROVVXIHRYMH-UHFFFAOYSA-N 0.000 description 1
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
- 125000002950 monocyclic group Chemical group 0.000 description 1
- WQEPLUUGTLDZJY-UHFFFAOYSA-N n-Pentadecanoic acid Natural products CCCCCCCCCCCCCCC(O)=O WQEPLUUGTLDZJY-UHFFFAOYSA-N 0.000 description 1
- 150000002812 neutral glycosphingolipids Chemical class 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 125000001181 organosilyl group Chemical group [SiH3]* 0.000 description 1
- DONJGKADZJEXRJ-UHFFFAOYSA-N pentadec-1-yne Chemical compound CCCCCCCCCCCCCC#C DONJGKADZJEXRJ-UHFFFAOYSA-N 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- TZLVRPLSVNESQC-UHFFFAOYSA-N potassium azide Chemical compound [K+].[N-]=[N+]=[N-] TZLVRPLSVNESQC-UHFFFAOYSA-N 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- 238000000039 preparative column chromatography Methods 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 230000001172 regenerating effect Effects 0.000 description 1
- 231100000241 scar Toxicity 0.000 description 1
- 230000037387 scars Effects 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- LKZMBDSASOBTPN-UHFFFAOYSA-L silver carbonate Substances [Ag].[O-]C([O-])=O LKZMBDSASOBTPN-UHFFFAOYSA-L 0.000 description 1
- 229910001958 silver carbonate Inorganic materials 0.000 description 1
- 229910001923 silver oxide Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
- 235000011121 sodium hydroxide Nutrition 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 238000006277 sulfonation reaction Methods 0.000 description 1
- 125000000472 sulfonyl group Chemical class *S(*)(=O)=O 0.000 description 1
- GFYHSKONPJXCDE-UHFFFAOYSA-N sym-collidine Natural products CC1=CN=C(C)C(C)=C1 GFYHSKONPJXCDE-UHFFFAOYSA-N 0.000 description 1
- 125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- 229940066528 trichloroacetate Drugs 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 1
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- FTVLMFQEYACZNP-UHFFFAOYSA-N trimethylsilyl trifluoromethanesulfonate Chemical compound C[Si](C)(C)OS(=O)(=O)C(F)(F)F FTVLMFQEYACZNP-UHFFFAOYSA-N 0.000 description 1
- FUMBGFNGBMYHGH-UHFFFAOYSA-M triphenyl(tetradecyl)phosphanium;bromide Chemical compound [Br-].C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(CCCCCCCCCCCCCC)C1=CC=CC=C1 FUMBGFNGBMYHGH-UHFFFAOYSA-M 0.000 description 1
- 231100000397 ulcer Toxicity 0.000 description 1
- 239000000052 vinegar Substances 0.000 description 1
- 235000021419 vinegar Nutrition 0.000 description 1
- 230000029663 wound healing Effects 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
- 235000005074 zinc chloride Nutrition 0.000 description 1
- 239000011592 zinc chloride Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H15/00—Compounds containing hydrocarbon or substituted hydrocarbon radicals directly attached to hetero atoms of saccharide radicals
- C07H15/02—Acyclic radicals, not substituted by cyclic structures
- C07H15/04—Acyclic radicals, not substituted by cyclic structures attached to an oxygen atom of the saccharide radical
- C07H15/10—Acyclic radicals, not substituted by cyclic structures attached to an oxygen atom of the saccharide radical containing unsaturated carbon-to-carbon bonds
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Biotechnology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Crystallography & Structural Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Saccharide Compounds (AREA)
Abstract
Ny fremgangsmåte til fremstilling av de i den europeiske patentsøknad nr. 146 810 beskrevne sphingosinderivatene av formelen. Den består i at man beskytter D-galactose i 4,6-stilling og oksyderer dette til tilsvarende, i ?., 4-stilling beskyttet D-threose, til sistnevnte kondenseres ved Wittig-reaksjon en alifatisk kjede (K 3), den frie hydroksylgruppen omvandles til en azidogruppe og beskyttelsesgruppen avspaltes, den oppnådde 2-azido-l,3-dihydroksyforbindelseri beskyttes selektivt i 1-stilling og blokkeres i 3-stilling, 1-hydroksygruppen settes igjen fri og den oppnådde forbindelsen eller den tidligere nevnte 2-azido-l,3-dihydroksyfor-bindelsen glykosideres med O-triluor- eller O-triklorazet-imidat eller 1-halogenderivåtet av en 2, 3,4,6-O-tetracyl-D-glukose, acylgruppene hhv. acylgruppene og beskyttelsesgruppen i 3-stilling avspaltes, azidogruppen overføres til en aininogruppe og aminoforbindelsen acyleres med en fettsyre R^-OH. Fremgangsmåten gir i realtivt få trinn forbindelsen fra den terapeutisk mest virksomme D-rekken uten adskillelse av diastereomerene og med godt utbytte.A new process for the preparation of the sphingosine derivatives of the formula described in European Patent Application No. 146,810. It consists in protecting D-galactose in the 4,6-position and oxidizing it to the corresponding, in?., 4-position protected D-threose, until the latter is condensed by Wittig reaction an aliphatic chain (K 3), the free the hydroxyl group is converted to an azido group and the protecting group is cleaved, the 2-azido-1,3-dihydroxy compound obtained is selectively protected in the 1-position and blocked in the 3-position, the 1-hydroxy group is left free and the obtained compound or the previously mentioned 2-azido The 1,3-dihydroxy compound is glycosided with the O-triluro- or O-trichloroazetimidate or 1-halogen derivative of a 2,3,4,6-O-tetracyl-D-glucose, the acyl groups or the acyl groups and the protecting group in the 3-position are cleaved, the azido group is transferred to an amino group and the amino compound is acylated with a fatty acid R The process gives in relatively few steps the compound from the therapeutically most effective D-series without separation of the diastereomers and with good yield.
Description
Gjenstand for den europeiske patentpublikasjon nr. 146 810 er nye sphingosinderivater av formelene: The subject matter of European Patent Publication No. 146,810 are new sphingosine derivatives of the formulas:
og fremgangsmåter til fremstilling derav. and methods for producing them.
I formelene ovenfor betyr R acylresten av en fettsyre med 14 til 24 karbonatomer, eller de tilsvarende acylrestene med en hydroksylgruppe i a-stilling eller med en eller to dobbeltbindinger i cis-konfigurasjon og R 2 star for pentadekanyl-eller heptadekanylresten eller tilsvarende C-^- og C-^-rester med en, to eller tre dobbeltbindinger, hvorav alltid en sitter i 1,2-stilling og oppviser trans-konfigurasjon, den eller de andre oppviser, når de er tilstede, cis-konfigurasjon. In the formulas above, R means the acyl residue of a fatty acid with 14 to 24 carbon atoms, or the corresponding acyl residues with a hydroxyl group in the a position or with one or two double bonds in the cis configuration and R 2 stands for the pentadecanyl or heptadecanyl residue or the corresponding C-^ - and C-^ residues with one, two or three double bonds, one of which always sits in the 1,2 position and exhibits trans configuration, the other one or more exhibit, when present, cis configuration.
Disse forbindelsene har erytrokonfigurasjon og tilsvarer de allerede kjente nøytrale glykosphingolipidene. De utmerker seg ved sårhelingsfremmende hhv. celle- og vevsregenererende egenskaper og egner seg for terapeutisk anvendelse ved sår av en hver genese, spesielt ved dårlig eller langsomthelende sår eller sårdannelser. I praksis fører de, spesielt ved topisk anvendelse på sår, til dannelse av friskt, nytt vev med god blodgjennomstrømming uten skjemmende arr. Fortrinnsvis anvendes sphingosinderivatene av formel (I)-D p.g.a. den These compounds have erythro configuration and correspond to the already known neutral glycosphingolipids. They excel at promoting wound healing or cell and tissue regenerating properties and is suitable for therapeutic use in wounds of any genesis, especially in poorly or slowly healing wounds or ulcers. In practice, they lead, especially when applied topically to wounds, to the formation of fresh, new tissue with good blood flow without unsightly scars. The sphingosine derivatives of formula (I)-D are preferably used because it
større terapeutiske virksomheten. larger therapeutic business.
Fremstillingen av de ovenfor omtalte forbindelsene tar utgangspunkt i tilsvarende ceramider av formelene: The preparation of the above-mentioned compounds is based on corresponding ceramides of the formulas:
Ceramidene kan på sin side fremstilles fra C-^g- eller C20-sphingosinene ved N-acylering ved hjelp av en fettsyre av formelen R^-OH. Avhengig av om det som utgangsprodukt anvendes en optisk aktiv eller en racemisk sphingosin far man forbindelsene av formel (I)-D eller (I)-L i optisk enhetlig form eller en blanding av diastereomerene (I)-D og (I)-L; i sistnevnte tilfelle må det på et bestemt fremgangsmåtetrinn foretas en adskillelse av diastereomerene. The ceramides, in turn, can be produced from the C-^g- or C-20-sphingosines by N-acylation using a fatty acid of the formula R^-OH. Depending on whether an optically active or a racemic sphingosine is used as starting product, the compounds of formula (I)-D or (I)-L are obtained in optically uniform form or a mixture of the diastereomers (I)-D and (I)-L ; in the latter case, a separation of the diastereomers must be carried out at a specific process step.
De racemiske sphingosinene har i den senere tid vist seg å kunne fremstilles med godt utbytte fra glycin ved en enkel syntes ifølge R.R. Schmidt og R. Klager [Angew. Chem. 94, 21-5-2I6- (1982); Angew. Chem. Int. Ed. Engl. 21,. 210-211 (1982); Angew.'. Chem. Suppl. 1982, 393-397 ]. Selv om den ovenfor nevnte fremstillingsfremgangsmåten gir sphingosinderivatene av formel (I)-D> eller (I)-L med tilfredsstillende utbytte ville en fremgangsmåte som kan gjennomføres uten adskillelse av diastereomerene være å foretrekke - når man tar i betraktning at de mest virksomme forbindelsene tilhørere D-rekken. The racemic sphingosines have recently been shown to be prepared with good yield from glycine by a simple synthesis according to R.R. Schmidt and R. Klager [Angew. Chem. 94, 21-5-2I6- (1982); Angew. Chem. Int Ed. English 21,. 210-211 (1982); Angew.'. Chem. Suppl. 1982, 393-397]. Even if the above-mentioned preparation method gives the sphingosine derivatives of formula (I)-D> or (I)-L in satisfactory yield, a method which can be carried out without separation of the diastereomers would be preferable - when one takes into account that the most effective compounds belong to The D series.
På den andre siden er forskjellige synteser kjente som, som 1utgangsprodukt, anvender en ad hoc valgt chiral forbindelse og som derved uten adskillelse av diastereomerene fører til de optisk aktive sphingosinene av erythro-konfigurasjon og D-rekken, følgelig til de i naturen forekommende sphingosinene. On the other hand, various syntheses are known which, as starting product, use an ad hoc chosen chiral compound and which thereby lead, without separation of the diastereomers, to the optically active sphingosines of erythro configuration and the D series, consequently to the naturally occurring sphingosines.
Den nå eldre syntesen ifølge E.J. Reist og P.H. Christie The now older synthesis according to E.J. Reist and P.H. Christie
[J. Org. Chem. 35, 3521 og 4127 (1970)], med utgangspunkt i D-glukose, og syntesen ifølge H. Newman [J. Am. Chem. Soc. [J. Org. Chem. 35, 3521 and 4127 (1970)], starting from D-glucose, and the synthesis according to H. Newman [J. Am. Chem. Soc.
95, 4098 (1973)] samt ifølge P. Tkaczuk og E.R. Thronton [J. Org. Chem. _46, 4393 (1981 )], begge med utgangspunkt i L-serin, inneholder alle et reaksjonstrinn med lavt utbytte, nemlig fremstillingen av 3-amino-3-desoksy-di-(O-isopropyliden)-a-D-allofuranose hhv. addisjonsreaksjonen for trans-vinylalan og et fra L-serin avledet aldehyd. 95, 4098 (1973)] as well as according to P. Tkaczuk and E.R. Thronton [J. Org. Chem. _46, 4393 (1981 )], both starting from L-serine, all contain a reaction step with a low yield, namely the production of 3-amino-3-deoxy-di-(O-isopropylidene)-α-D-allofuranose or the addition reaction for trans-vinylalanine and an aldehyde derived from L-serine.
En nyere syntese ifølge B. Bernet og A. Vasella [Tetrahedron Letters 24, 5491-5494 (1983)] gir D-erythro-Clg-sphingosin etter 6 reaksjonstrinn med et samlet utbytte på 33%. Syntesen tar riktignok utgangspunkt i den ikke lett tilgjengelige forbindelsen pentadecyn, hvis fremstilling har negativ innvirk-ning på antallet trinn og det samlede utbyttet. A more recent synthesis according to B. Bernet and A. Vasella [Tetrahedron Letters 24, 5491-5494 (1983)] gives D-erythro-Clg-sphingosine after 6 reaction steps with an overall yield of 33%. The synthesis is admittedly based on the not easily available compound pentadecyne, the production of which has a negative effect on the number of steps and the overall yield.
Til sist skal også syntesen av ceramid ifølge K. Koike, Y. Nakahara og T. Ogawa [Glycoconjugate J. 1, 107-109 (1984)] nevnes, som tar utgangspunkt i et D-glykosederivat, omfatter 12 reaksjonstrinn og gir ceramidet med et utbytte på ca. 20%. Fremgangsmåten burde kunne anvendes til fremstilling av sphingosinene av naturlig konfigurasjon. Finally, the synthesis of ceramide according to K. Koike, Y. Nakahara and T. Ogawa [Glycoconjugate J. 1, 107-109 (1984)] should also be mentioned, which starts from a D-glucose derivative, comprises 12 reaction steps and gives the ceramide with a dividend of approx. 20%. The method should be able to be used for the production of the sphingosines of natural configuration.
Ved den innledningsvis omtalte fremstillingene av sphingosinderivater av formelen (I)-D har også den hittil i og for seg fordelaktige anvendelsen av de optisk aktive D-sphingosinene som utgangsprodukter vært påvirket i negativ retning av deres arbeidsmessig omstendelige og/eller utbyttemessig utilfreds-stillende fremstilling. In the production of sphingosine derivatives of the formula (I)-D mentioned at the outset, the hitherto in and of itself advantageous use of the optically active D-sphingosines as starting products has also been negatively affected by their labor-intensive and/or yield-unsatisfying preparation .
Det er nå funnet at man kan oppnå optisk enhetlige sphingosinderivater av formel (I) It has now been found that optically uniform sphingosine derivatives of formula (I) can be obtained
ved en ny fremgangsmåte, som tar utgangspunkt i kommersielt tilgjengelig D-galactose, omfatter totalt 9 hhv. 12 trinn og gir de ønskede forbindelsene med et tilfredsstillende totalutbytte. I formelen (I) betyr R1 den samme acylresten som angitt ovenfor v så beskrivelsen av formelene (I)-D og (I)-L, mens R 3' er en alifatisk rest med 13 til 19 karbonatomer, hvorav minst 13: foreligger i rett kjede og eventuelt høyst 4 som sidestående metylgrupper, denne resten kan inneholde inntil tre dobbeltbindinger av cis- eller trans-konfigurasjon eller inntil tre trippelbindinger. by a new method, which is based on commercially available D-galactose, comprises a total of 9 or 12 steps and gives the desired compounds with a satisfactory total yield. In the formula (I) R1 means the same acyl residue as stated above v then the description of the formulas (I)-D and (I)-L, while R 3' is an aliphatic residue with 13 to 19 carbon atoms, of which at least 13: are present in straight chain and optionally at most 4 as adjacent methyl groups, this residue can contain up to three double bonds of cis- or trans-configuration or up to three triple bonds.
Fremgangsmåten ifølge oppfinnelsen består i at man omsetter D-galactose med et lavere alifatisk keton eller et aromatisk aldehyd av formelen R-CO-R', hvori R og R' begge står. for en lavere alkylrest hhv. står R og R' for hydrogenatomet og den andre for en aromatisk rest, til en i 4- og 6-stilling beskyttet D-galactose av formel (II), denne forbindelsen oppspaltes med et oksydasjonsmiddel som spalter nabostående dioler, til tilsvarende, i 2- og 4-stillingene beskyttet D-threose av formel (III), den beskyttede D-threosen omsettes med et R^-CH^-fosfonat eller ec R 3 -Cr^-trifenylfosfoniumhalogenid, hvori R 3har den ovenfor angitte betydning, i nærvær av en base hhv. en base og The method according to the invention consists in reacting D-galactose with a lower aliphatic ketone or an aromatic aldehyde of the formula R-CO-R', in which R and R' both stand. for a lower alkyl residue or R and R' stand for the hydrogen atom and the other for an aromatic residue, to a D-galactose protected in the 4- and 6-position of formula (II), this compound is cleaved with an oxidizing agent that cleaves neighboring diols, to the equivalent, in 2 - and the 4-positions of protected D-threose of formula (III), the protected D-threose is reacted with an R^-CH^-phosphonate or ec R 3 -Cr^-triphenylphosphonium halide, wherein R 3 has the above meaning, in the presence of a base or a base and
et salt til en forbindelsen av formelen (IV), den frie hydrok-i sylgruppen i denne forbindelsen overføres ved aktivering til en azidogruppe, den oppnådde azidoforbindelsen av formel (V) befris for beskyttelsesgruppen for hydroksylgruppen i 1- og 3-stillingene på den alifatiske kjeden under dannelse av en 2- a salt of a compound of formula (IV), the free hydroxyl group in this compound is transferred by activation to an azido group, the obtained azido compound of formula (V) is freed from the protecting group for the hydroxyl group in the 1- and 3-positions of the aliphatic chain while forming a 2-
azido-1,3-dihydroksyforbindelse av formelen (VI), sistnevnte omsettes med en organisk reagens, som kan reagere selektivt azido-1,3-dihydroxy compound of the formula (VI), the latter is reacted with an organic reagent, which can react selectively
med en primær hydroksylgruppe, under dannelse av en forbindelse with a primary hydroxyl group, forming a compound
av formel (VIII), hvori R" står for en hydroksylbeskyttelsesgruppe, i forbindelsen av formel (VIII) blokkeres den sekundære hydroksylgruppen med beskyttelsesgruppe R"', fra den oppnådde forbindelsen av formel (IX) avspaltes hydroksylbeskyttelsesgruppen R" under dannelse av en forbindelse av formelen (X), of formula (VIII), in which R" stands for a hydroxyl protecting group, in the compound of formula (VIII) the secondary hydroxyl group is blocked with protecting group R"', from the obtained compound of formula (IX) the hydroxyl protecting group R" is cleaved to form a compound of the formula (X),
og enten den tidligere oppnådde forbindelsen av formelen (VI) eller forbindelsen av formelen (X) glykoksideres med O-trifluor-eller O-triklor-acetatet eller 1-halogenderivatet av en D-glucose, hvis hydroksylgrupper i 2-, 3-, 4- og 6-stillingene er beskyttet med acylrester Ac, til en forbindelse av formelen (VII) hhv. and either the previously obtained compound of formula (VI) or the compound of formula (X) is glycooxidized with the O-trifluoro- or O-trichloro-acetate or the 1-halogen derivative of a D-glucose, whose hydroxyl groups in 2-, 3-, 4 - and the 6-positions are protected with acyl residues Ac, to a compound of the formula (VII) or
(XI), fra den oppnådde forbindelsen avspaltes acylgruppene Ac hhv. acylgruppene Ac og beskyttelsesgruppen R"' under dannelse av den samme forbindelsen av formelen (XII), i denne overføres azidogruppen til en primær aminogruppe og den oppnådde forbindelsen av formelen (XIII) underkastes en N-acylering med en fettsyre av formelen R^-OH. (XI), from the obtained compound the acyl groups Ac or the acyl groups Ac and the protecting group R"' forming the same compound of the formula (XII), in which the azido group is transferred to a primary amino group and the obtained compound of the formula (XIII) is subjected to an N-acylation with a fatty acid of the formula R^-OH .
i in
I det følgende skal oppfinnelsen beskrives mer utførlig. In what follows, the invention will be described in more detail.
Den organiske karboksylsyren R^OH, hvorfra acylgruppen R<1> i sphingosinderivatene av formel (I) er avledet, er eksempelvis i myristinsyren <c>i4H2<g>°2' Palmitinsyren C2gH3202' stearinsyren <C>18<H>36°2' olJesyre<n><c>i8Hj2°2' linolsyren' C18H32°2' arachinsYren <C>20<H>40°2' benensyren C22H44°2 og ~ ved den øvre grensen av den for R angitte betydning - tetracosansyren (1ignocerinsyre) C24<H>48°2' cis_15~tetracosensyre (nervonsyr<e>) <C>24<H>46°2' <2->nydroksy" itetracosansyre (cerebronsyre) C24H48°3' 2-nydroksy-15-tetra-cosensyre (hydroksynervonsyre) <C>24H46°3 og 2-hydroksy-17-tetra-cosensyre som er isomer med sistnevnte. The organic carboxylic acid R^OH, from which the acyl group R<1> in the sphingosine derivatives of formula (I) is derived, is for example in myristic acid <c>i4H2<g>°2' Palmitic acid C2gH3202' stearic acid <C>18<H>36° 2' oleic acid <n><c>i8Hj2°2' linoleic acid' C18H32°2' arachinic acid <C>20<H>40°2' benenic acid C22H44°2 and ~ at the upper limit of the meaning given for R - tetracosanoic acid ( 1ignoceric acid) C24<H>48°2' cis_15~tetracosenoic acid (nervonic acid<e>) <C>24<H>46°2' <2->nydroxy" itetracosanoic acid (cerebronic acid) C24H48°3' 2-nydroxy-15- tetra-cosenoic acid (hydroxynervonic acid) <C>24H46°3 and 2-hydroxy-17-tetra-cosenoic acid which is isomeric with the latter.
Den alifatiske resten R 3kan være en uforgrenet kjede eller 5bære en, to, tre eller fire metylgrupper som substituenter. Videre kan kjeden være mettet eller umettet; i sistnevnte tilfelle oppviser den en til tre dobbeltbindinger hhv. en til tre trippelbindinger. Dobbeltbindingene har cis- eller trans-konfigurasjonen. Foretrukne alifatiske rester R 3 er rester med ulike antall karbonatomer, spesielt C^- og C15~restene. The aliphatic radical R 3 can be an unbranched chain or bear one, two, three or four methyl groups as substituents. Furthermore, the chain can be saturated or unsaturated; in the latter case, it exhibits one to three double bonds, respectively. one to three triple bonds. The double bonds have the cis or trans configuration. Preferred aliphatic residues R 3 are residues with different numbers of carbon atoms, especially the C^ and C 15 residues.
Ved det første trinnet i fremgangsmåten kan man til beskyttelse At the first step in the procedure one can go to protection
av hydroksylgruppene i 4- og 6-stilling på D-galactose anvende et lavere alifatisk keton som aceton, etylmetylketon eller dietylketon, eller et aldehyd fra den aromatiske rekken som benzaldehyd eller et på fenylringen substituert benzaldehyd. Foretrukket er anvendelsen av benzaldehydet. Som kondensasjons-middel for reaksjonen egner seg generelt Lewissyrer, som zinkklorid, bortrifluorid, aluminiumklorid og jernklorid, eller Brønsted-syrer som p-toluensulfonsyre. Overføringen av D-galactosen til 4,6-0-benzyliden-D-g,alactose kan f. eks. gjennomføres ved fremgangsmåten ifølge E.G. Gros og V. Deulofeu [J. Org. Chem. 29, "647-3654 (1964)], omsetningen av D-galactose med aceton til 4,6-O-isopropyliden-D-galactose kan foretas ved fremgangsmåten ifølge J. Gelas og D. Horton [Carbohydr. Res. 71, 103-121 (1979)]. of the hydroxyl groups in the 4- and 6-position on D-galactose use a lower aliphatic ketone such as acetone, ethyl methyl ketone or diethyl ketone, or an aldehyde from the aromatic series such as benzaldehyde or a benzaldehyde substituted on the phenyl ring. The use of the benzaldehyde is preferred. Lewis acids, such as zinc chloride, boron trifluoride, aluminum chloride and ferric chloride, or Brønsted acids such as p-toluenesulfonic acid are generally suitable as condensation agents for the reaction. The transfer of the D-galactose to 4,6-0-benzylidene-D-g,alactose can e.g. carried out by the method according to E.G. Gros and V. Deulofeu [J. Org. Chem. 29, "647-3654 (1964)], the reaction of D-galactose with acetone to 4,6-O-isopropylidene-D-galactose can be carried out by the method according to J. Gelas and D. Horton [Carbohydr. Res. 71, 103 -121 (1979)].
Det i det andre fremgangsmåtetrinnet anvendte oksydasjons- The oxidation used in the second method step
midlet kan være et alkalimetallperjodat, f.eks. litium-, the agent may be an alkali metal periodate, e.g. lithium,
natrium- eller kaliumsaltet, eller blytetraacetat; fortrinns- the sodium or potassium salt, or lead tetraacetate; preferential
vis anvendes natriumperjodat. Oksydasjonen gjennomføres med fordel ved en pH-verdi på 7 til 8, f.eks. i en tilsvarende sodium periodate is used. The oxidation is advantageously carried out at a pH value of 7 to 8, e.g. in a corresponding
■bufferoppløsning, og ved romtemperatur. ■buffer solution, and at room temperature.
Wittig-reaksjonen ifølge det tredje fremgangsmåtetrinnet gjennom-føres som regel i en inertgassatmosfære, f.eks. under nitrogen, ved lave temperaturer, f.eks. ved -10 til -20°C, og ved anvendelse av et R<3->CH2~fosfoniumhalogenid i nærvær av et salt, f.eks. litiumbromid, natriumklorid eller kaliumbromid. Som base egner seg bl..a. organiske litiumforbindelser, spesielt fenyllitium eller litiummetylat, videre natriumamid, natriummetylat og natriumkarbonat. Som oppløsningsmiddel kan man :anvende aromatiske hydrokarboner som benzen, toluen eller The Wittig reaction according to the third method step is usually carried out in an inert gas atmosphere, e.g. under nitrogen, at low temperatures, e.g. at -10 to -20°C, and using a R<3->CH2~phosphonium halide in the presence of a salt, e.g. lithium bromide, sodium chloride or potassium bromide. As a base, suitable, among other things, organic lithium compounds, especially phenyllithium or lithium methylate, further sodium amide, sodium methylate and sodium carbonate. Aromatic hydrocarbons such as benzene, toluene or
xylen, eller etere som dietyleter, tetrahydrofuran eller dioksan; oppløsningsmidlet må være vannfritt. xylene, or ethers such as diethyl ether, tetrahydrofuran or dioxane; the solvent must be anhydrous.
Overføringen av den frie hydroksylgruppen til en azidogruppe ved aktivering kan med fordel gjennomføres ved O-sulfoner ing av forbindelsen (IV) og etterfølgende omsetning av det dannede O-sulfonylderivatet, f.eks. metansulfonyl-, trifluormetan^ sulfonyl- eller p-toluensulfonylderivatet; derved foregår en •inversjonav konfigurasjonen ved C2D-threose. O-sulfoner ingen kan gjennomføres ved fremgangsmåtene beskrevet i "Ullmanns Encyklopadie der technischen Chemie", 4. opplag, bind 11, The transfer of the free hydroxyl group to an azido group upon activation can advantageously be carried out by O-sulfonation of the compound (IV) and subsequent reaction of the formed O-sulfonyl derivative, e.g. the methanesulfonyl, trifluoromethane, sulfonyl or p-toluenesulfonyl derivative; thereby an •inversion of the configuration takes place at C2D-threose. O-sulfones none can be carried out by the methods described in "Ullmann's Encyklopadie der technischen Chemie", 4th edition, volume 11,
side 91, Verlag Chemie GmbH, Weinheim BRD (1976). Man anvender som regel et syrehalogenid eller et syreanhydrid av en lavere alifatisk sulfonsyre eller en monocyklisk aromatisk sulfonsyre, eksempelvis metansulfonylklorid, p-toluensulfonylklorid, metansulfonsyreanhydrid eller trifluormetansulfonsyreanhydrid. O-sulfoner ingen gjennomføres fortrinnsvis i nærvær av en base. Idet vannfrie reaksjonsbetingelser skal opprettholdes og et organisk oppløsningsmiddel anvendes som f . eks.' benzen, toluen, tetrahydrofuran, dietyleter eller diklormetan, egner seg som base spesielt tertiære organiske baser som trietylamin, dimetylanilin, pyridin, collidin, lutidin o.l. Den etterfølgende omsetningen med alkalimetallazidet, f.eks. litium-, natrium-eller kaliumazid, gjennomføres med fordel uten rensing av 0-sulfonylderivatet. Begge reaksjonene gjennomføres fortrinnsvis i en inertgassatmosfære, f.eks. under nitrogen, og ved lave temperaturer eller romtemperatur. page 91, Verlag Chemie GmbH, Weinheim BRD (1976). As a rule, an acid halide or an acid anhydride of a lower aliphatic sulphonic acid or a monocyclic aromatic sulphonic acid is used, for example methanesulphonyl chloride, p-toluenesulphonyl chloride, methanesulphonic anhydride or trifluoromethanesulphonic anhydride. O-sulfones are preferably carried out in the presence of a base. As anhydrous reaction conditions are to be maintained and an organic solvent is used such as eg.' benzene, toluene, tetrahydrofuran, diethyl ether or dichloromethane, particularly tertiary organic bases such as triethylamine, dimethylaniline, pyridine, collidine, lutidine etc. are suitable as bases. The subsequent reaction with the alkali metal azide, e.g. lithium, sodium or potassium azide, is advantageously carried out without purification of the 0-sulfonyl derivative. Both reactions are preferably carried out in an inert gas atmosphere, e.g. under nitrogen, and at low temperatures or room temperature.
I det femte fremgangsmåtetrinnet kan avspaltningen av beskyttelsesgruppen fra forbindelsen (V) foregå ved sur hydrolyse. Eksempelvis oppløser man forbindelsen i et organisk oppløsnings-middel som diklormetan eller dimetylformamid og lar så en liten ,mengde konsentrert saltsyre eller vann innvirke en viss tid, fortrinnsvis ved romtemperatur. In the fifth method step, the removal of the protective group from the compound (V) can take place by acid hydrolysis. For example, the compound is dissolved in an organic solvent such as dichloromethane or dimethylformamide and then a small amount of concentrated hydrochloric acid or water is allowed to act for a certain time, preferably at room temperature.
Nå kan forbindelsen (VI) direkte underkastes glykoksyderingen under dannelse av en forbindelse (VII), eller den kan via ;mellomproduktene (VIII), (IX) og (X) omvandles til en forbindelse (XI), som så underkastes glykoksidering. Denne andre fremgangsmåtevarianten omfatter riktignok tre reaksjonstrinn mer, den gir imidlertid et høyere totalutbytte og egner seg derfor spesielt godt for en produksjon i industriell målestokk. Now the compound (VI) can be directly subjected to the glycooxidation to form a compound (VII), or it can be converted via the intermediates (VIII), (IX) and (X) into a compound (XI), which is then subjected to glycooxidation. This second process variant does indeed comprise three more reaction steps, but it gives a higher total yield and is therefore particularly suitable for production on an industrial scale.
Den skal beskrives nærmere i det følgende. It shall be described in more detail below.
Beskyttelsen av den primære hydroksylgruppen i R-azido-1,3-dihydroksyforbindelsen (VI) skal foretas med reagenser som i nærvær av en primær og en sekundær hydroksylgruppe reagerer selektivt med førstnevnte. Som beskyttelsesgruppe R" egner seg spesielt grupper som stiller store romlige krav, som f.eks. tert.butyl-, trifenylmetyl- (trityl-), trikloracetyl-, trimetylsilyl-, tert.butyldimetylsilyl- eller tert.butyldi-fenylsilylgrupper. Foretrukket er trifenylmetyl-, monometoksy-trifenylmetyl-, tert.butyldimetylsilyl- og tert.butyldiferuyl-silylgruppene. The protection of the primary hydroxyl group in the R-azido-1,3-dihydroxy compound (VI) must be carried out with reagents which, in the presence of a primary and a secondary hydroxyl group, react selectively with the former. As protecting group R", groups that make large spatial demands are particularly suitable, such as, for example, tert.butyl, triphenylmethyl (trityl), trichloroacetyl, trimethylsilyl, tert.butyldimethylsilyl or tert.butyldiphenylsilyl groups. Preference is given to the triphenylmethyl, monomethoxy-triphenylmethyl, tert-butyldimethylsilyl and tert-butyldiferuylsilyl groups.
Innføringen av beskyttelsesgruppen R" foregår ved de kjente i fremgangsmåtene innen organisk kjemi, svarende til typen av den valgte beskyttelsesgruppen. Eksempelvis kan trifenylmetyl-gruppen innføres ved behandling av ceramidet med et tilsvarende halogenid som trifenylklormetan eller trifenylbrommetan. Også fo:r: tert.butyldimetylsilyl- og tert.butyldifenylsilylgruppen kam det tilsvarende nalogenide^t.,, f.o>rtrimnsvis kloridet elle* bromidet med fordel anvendes. ;Deretter beskyttes den i 1-stilling beskyttede forbindelsen av formel (VIII) ved hydroksylgruppen i 3-stilling med en beskyttel-rsesgruppe R"', f.eks. ved forestring med en organisk karboksylsyre Ac'OH eller et reaktivt funksjonelt derivat derav. Frem for alt egner seg for dette formålet enkle, alifatiske karbok-sylsyrer og aromatiske, spesielt monocykliske aromatiske kar-boksylsyrer.;. foretrukket er anvendelsen av benzosyre, en substituert benzosyre eller pivalinsyre. ;Forestringen med karboksylsyren Ac'OH kan gjennomføres ved fremgangsmåtene beskrevet i "Ullmanns Encyklopadie der technischen Chemie", 4. opplag, bind 11, side 91, Verlag Chemie GmbH, 5Weinheim BRD' (1976). Den foregår med fordel under anvendelse ;av et karboksylsyrehalogenid i nærvær av en tertiær organisk base som trietylamin, pyridin eller dimetylanilin, i et vannfritt organisk oppløsningsmiddel, som benzen, toluen, tetrahydrofuran, dietyleter eller diklormetan. ;Beskyttelsesgruppen R" på hydroksylgruppen i 1-stilling i forbindelsen av formelen (IX) kan avspaltes ved sur hydrolyse ;(trifenylmetylbeskyttelsesgrupper, silylbeskyttelsesgrupper ) ;eller ved behandling med bortrifluorid-eterat (trifenylmetyl-grupper). Man får forbindelsen av formel (x) hvori hydroksylgruppen i 3-stilling er blokkert av beskyttelsesgruppen k"<1>, ;men den primære hydroksylgruppen i 1-stilling er igjen fri. ;Omsetningen av forbindelsen (IX) eller forbindelsen (VI) med O-triklor- eller O-trifluor-acetimidatet av en D-glukose, hvis hydroksylgrupper i tillegg til den ved 1-stillingen er beskyttet ved hjelp av acylrester Ac, katalyseres med fordel ved hjelp av en Lewissyre som bortrifluorideterat eller trifluormetan-sulfonsyretrimetylsilylester. Den gjennomføres generelt i et vannfritt organisk oppløsningsmiddel som et hydrokarbon (heksan) eller et halogenert hydrokarbon (diklormetan). ;Som acylrester til beskyttelse av hydroksylgruppene i 2-, ;3-, 4- og 6-stillingene i D-glukose anvendes fortrinnsvis lavere alifatiske acylgrupper som acetyl-, propionyl-, pivaloyl-, trifluoracetyl- eller metansulfonylgrupper. Enkeltheter ved-rørende fremstillingen av reagensen kan finnes i avhandlingen til R.R. Schmidt og M. Stumpp (Liebigs Ann. Chem. 1983, 1249-1256) og R.R. Schmidt, J. Michel og M. Roos (Liebigs Ann. Chem. 1984, 1343-1357). ;Den tilsvarende omsetningen med 1-halogenderivåtet av den O-tetraacylerte D-glukosen eksempelvis med O-acetyl-a-D-glucopyranosylklorid eller -bromid (sistnevnte også betegnet a-D-O-acetobromglukose;, gjennomføres som regel i nærvær av en tungmetallforbindelse som sølvoksyd, et tungmetallsalt, som sølvkarbonat eller kvikksølvcyanid, eller en organisk base, ;som fungerer som syrebindende middel ("Ullmanns Encyklopadie der technischen Chemie", 4. opplag, bind 24, side 757, Verlag Chemie GmbH, Weinheim BRD 1983). ;Avspaltningen av acylrestene Ac og beskyttelsesgruppen R"<1>;fra forbindelsen (VII) hhv. (XI) katalyseres generelt ved hjelp av baser; spesielt hensiktsmessig for dette formålet er anvendelsen av natriummetanolat i vannfri metanol ved romtemperatur . ;I det nest siste fremgangsmåtetrinnet tilveiebringes overføringen av azidogruppen til den primære aminogruppen best ved behandling av forbindelsen (XIImed hydrogensulfid ved ;romtemperatur. For dette formålet oppløses forbindelsen eksempelvis i en blanding (1:1) av vann og pyridin. Denne overføringen kan også gjennomføires ved hydrering med natriumborhydrid eller med et annet reduksjonsmiddel, som f.eks. natriumcyanoborhydrid. ;N-acyTeringen av forbindelsen (XIII) med d!e.n org>aniske karboksylsyren av formelen R -0H (siste1 £iemg;ang;s.måtet.rinni> Icara gjennomføres ved fremgangsmåten ifølge D. Shapiro og; ;medarbeidere [J. Am. Chem. Soc. 86, 4472 (1964)]. Generelt anvender man karboksylsyren selv i nærvær av et vannavspaltende middel, som dicykloheksylkarbodiimid i diklormetan, eller et funksjonelt reaktivt derivat av karboksylsyren, som en aktivert ester eller et halogenid i nærvær av en uorganisk base som natriumacetat eller en tertiær organisk base. N-acyleringen gjennomføres med fordel ved romtemperatur. ;Isoleringen og rensingen av forbindelsene som oppstår på hvert f remgangsmåtetr inn foregår ved kjente f remg,ang<'sm'åter innen den organiske kjemien. ;De følgende eksemplene anskueliggjør foretrukne utførelses-former for oppfinnelsen. ;<1>H-NMR-spektrene ble målt med 250 MHz-instrumentet "WM 250 Cryospec" for firma Bruker, Spectrospin, Industriestrasse 26, CH-8117 Fallanden/ziirich. Forskyvningene er angitt på basis ;av tetrametylsilan (TMS) som indre standard og angitt i ppm. ;De angitte smeltepunktene er bestemt på en kobberblokk og er ;ikke korrigert. ;Til analytisk tynnsjiktkromatografi (DC) ble det anvendt kisel-gelplater fra firma E. Merck AG, Darmstadt, (BRD). Tynnsjikt-kromatogrammene ble, så sant stoffene ikke var UV-aktive, sprøytet med 15% svovelsyre og fremkalt ved 120°C. ;Preparativ søylekromatografi ble gjennomført med "Kieselgel 60" ;(0,062-0,200 mm) fra firma Merck. For mellomtrykkskromatografi ble det anvendt ferdigsøyler ifølge D. Flockerzi, Diplomarbeit, Universitat Stuttgart/BRD (1978), med kiselgel "LiChroprep Si ;60, 15-25". ;Utbyttene ble angitt på det rensetrinnet hvor NMR-spektroskopisk og ved hjelp av tynnsjiktkromatografi ingen forurensninger lenger kunne påvises. ;i ;Ved oppløsningsmiddelblandingene betyr angivelsene i parentes ;volumdeler. ;Eksempel 1 ;2S, 3R- 2- heksadekanoylamino- 3- hydroksy- l-( B- D- glukopyranosyloksy)-i ;4- trans- eikosen ;a) 4, 6- 0- benzyliden- D- galactose ;Se J. Org. Che. 29, 3647-3654 (1964). ;D ;b) 2, 4- O- benzyliden- D- threose (1) ;30 g (0,111 mol) 4,6-O-benzyliden-D-galactose oppløses i ;ca. 1 200 ml fosfatbuffer av pH 7,6. 55 g (0,257 mol) ;natriumperjodat tilsettes under kraftig omrøring. pH- ;5verdien holdes ved dråpevis tilsats av 2N natronlut på ca. ;7 til 8. Det omrøres i 1,5 timer ved romtemperatur. Deretter inndampes det i vannstrålevakuum til tørrhet. Den faste resten ekstraheres 4 ganger, hver gang med 250 ml ;eddikester. Ektraktet filtreres, tørkes over magnesiumsulfat og inndampes. Utbytte: 20 g (85%), Rp=0,64 i toluen/etanol (3:1). ;c) 2S, 3R- 1, 3- 0- benzyliden- 2- hydroksy- 4- trans- eikosen (2) ;70 g (0,12 mol) heksadecyltrifenylfosfoniumbromid suspen-deres under nitrogen i ca. 1 liter vannfri toluen mettet ;med nitrogen. Fenyllitium, fremstilt fra 6,5 g (0,94 mol) litium og 74 g (0,47 mol) brombenzen i ca. 200 ml vannfri eter, tilsettes dråpevis uten ytterligere rensing. Sam- ;tidig avkjøles blandingen til -15°C. Deretter tilsettes dråpevis 20 g (0,096 mol) av forbindelse (1) i ca. 150 ml vannfri tetrahydrofuran under nitrogen i løpet av 20 minutter. Etter ytterligere 20 minutter tilsettes først 150 ml metanol og deretter 250 ml. vann. Det omrøres kraftig. Den organiske fasen inndampes etter fraskillelse av den vandige fasen. ;For rensing kromatograferes over kiselgel med petroleumseter/eddikester (9:1). Utbytte 27 g (68%), R r=0,21 i petroleumseter/eddikester (9:1). ;d) 2S, 3R- 2- Azido— 1, 3- 0- benzyliden- 4- trans- eikosen (3) ;10 g (0,025 mol) av forbindelsen (2) oppløses i ca. 70 ;ml vannfri diklormetan, som inneholder 5 ml vannfritt pyridin. Det avkjøles under nitrogen til -15°C. 8,12 g (0,029 mol) tr if luormetansulf onsyrean<h\ydir.id tilsettes langsomt og dråpevis. Etter 15 mi mutter filtreres; over kiselgel og elueres med. dikloone.tan/pe.tr.oleumseter (1:1);. Blandingen spyles stadig; med. nitrogen. Det. inndampes og den tilbakebiivende- oljen» opptas; i 50'- ml vannfritt di-metylf ormamid. Under, nitrogen til settes. 7,5 g (0,1 mol) natriumazid.. Det omrøres i 2 timer ved romtemperatur. Deretter fortynnes det med ca. 350 ml diklormetan, filtreres og inndampes i vannstrålevakuum. For re.ns.inig, kromatografer.es over kiselgel med petroleumseter/eddikester (9:1). Utbytte: 8 g (75%), R.p=0,8 i petroleumseter/eddikester (9:1). ;e) 2S, 3R- 2- azido- l, 3- dihydroksy- 4- trans- eikosen (4) ;8 g (0,018 mol) av forbindelse (3) oppløses i 100 ml ;diklormetan. Det tilsettes 5 ml konsentrert saltsyre og 3 ml vann og omrøres kraftig ved romtemperatur i 12 timer. Deretter utristes med vandig natriumhydrogenkarbo-natoppløsning. Den organiske fasen fraskilles, tørkes over natriumsulfat og inndampes. For rensing kromatograferes over kiselgel med diklormetan/metanol ' ( 95 : 5 ) .. Utbytte: 4,32 g (68%), R r=0,46 i diklormetan/inetanol (95:5), smeltepunkt 56-57°C. ;Elementæranalyse: beregnet C 67,95 H 11,11 N 11,88 ;funnet 67,62 11,12 11,85 ;<1>H-NMR (250 MHz, CDC13 i ppm) forbindelse (4): 5,83 (m, 1H, -CH2-CH=C); 5,55 (dd, 1H, -CH2-CH=CH-, J = 15,5 Hz, ;J = 6,5 Hz); 4,25 (m, 1H, -CH-N3); 3,8 (m, 2H, -CH_2-OH, CH-OH); 3,52 (m, 1H, -CH2-OH); 2,05 (m, 4H, OH, C=CH-CH2 ) ; ;1,45-1,18 (m, 26H, alifat.); 0,88 (t, 3H, CH3) . ;f) 2S, 3R- 2- azido- 2- hydroksy- l-( 2, 3, 4, 6- tetra- O- acetyl- B-D- qlukopyranosyloksy_) - 4- trans- eikosen ( 6 ) ;0,5 g (1,41 mmol) av foroindelse (4) oppløses i 50 ml vannfri heksan. Det tilsettes 0,1 ml 0,5 M bortrifluorid-eterat i diklormetan og en spatelspiss molekylarsikt 4 Å. 0,7 g (1,41mmol ) O-(2,3,4,6-tetra-O-acetyl-a-D-gluko-pyranosyl)-trikloracetimidat oppløses i 3ml vannfri toluen og tilsettes langsomt dråpevis. Etter 4 timer vaskes med 30 ml mettet natriumhydrogenkarbonatoppløsning. Den vandige ;fasen utristes 3 ganger, hver gang med 30 ml diklormetan. De organiske fasene tørkes over natriumsulfat og inndampes. For rensing kromatograferes over kiselgel med diklormetan/ metanol (97,5:2,5). Utbytte: 0,385 g (40%), Rp=0,7 i ;diklormetan/metanol (95:5). ;<1>H-NMR (250 MHz, CDC13 i ppm) forbindelse (6): 5,78 (m, 1H, -CH2-CH=C); 5,5 (dd, lfl, -Cri2~CH=CH, J = 15,5 Hz, J = 7,3 Hz); 5,3-4,98 (m, 3H, H-2, H-3, H-4); 4,58 (d, 1H, H-l, ;J = 7,6 Hz); 4,35-4,13 (m, 3H, H-6, H-6; -CH-N3); 4,05 (dd, 1H, -CH2-0-); 3,73 (m, 2H, H-5, -CH2~0); 3,47 (m, 1H, ;■;CH-OH); 2,24 (d, 1H, OH, J = 4,8 Hz); 2,16-1,94 (m, 14H, acetyl, C=CH-CH_2); 1,45-1,15 (m, 26H, alifat.); 0,88 (t, 3H, -Cfl3). ;g ) 2S„- 3R- 2- azido- 3- hydroksy- l-( B- D- glukopyranosyloksy)- 4-trans- eikosen (7 ) ;0,4 g (0,585 mmol) av forbindelse (6) oppløses i 30 ml vannfri metanol. Det tilsettes 0,2 ml av IM oppløsning av ;natriummetylat i metanol. Det omrøres i 1 time ved romtemperatur. Deretter nøytraliseres det med ioneveksleren "Amberlite IR 120" (H+<->form). Ioneveksleren frafiltreres, det inndampes og kromatograferes over kiselgel med kloroform/metanol (9:1). Utbytte: 0,26 g (86%), R =0,22 i ;kloroform/metanol (9:1). ;<1>H-NMR (250 MHz, DMSO-d6 i ppm) forbindelse (7): 4,10 (d, 1H, H-l, J=7,6 Hz). ;h) 2S, 3R- 2- amino- 3- hydroksy- l-( B- D- glukopyranosyloksy)- 4-trans- eikosen (8) ;0,26 g (0,5 mmol) av forbindelse (7) oppløses i en blanding av 4 ml pyridin og 4 ml vann. Oppløsningen mettes med hydrogensulfid. Det omrøres i 24 timer ved romtemperatur. Det inndampes til tørrhet og kromatograferes over kiselgel først med kloroform/metanol (6:4), deretter med kloroform/ metanol/vann (5:4:1). Utbytte: 0,234 g (96%), R r=0,65 i kloroform/metanol/vann (5:4::1). ;^H-NMR (250 MHz,;DMSO-d6 i ppm) forbindelse (8): 4,10 ;(d, IK, H-l, J = 7,6 Hz). ;i) 2S, 3R- 2- heksadekanoylamino- 3- hydroksy- l-( 8- D^ glukopyrano-sy1oksy)- 4- trans- eikosen (9) ;0,23 g (0,47 mmol) av forbindelse (8) oppløses i 5 ml tetrahydrofuran. 5 ml av en 50% vandig natriumacetat-oppløsning tilsettes. Blandingen blandes ved romtemperatur under kraftig omrøring med 0,19 g (0,7 mmol) heksadekanoyl-klorid. Etter ca. 2 timer fraskilles den organiske fasen. Den vandige fasen utristes 3 ganger, hver gang med 2 ml kloroform. Den organiske fasen tørkes over natriumsulfat og inndampes. For rensing kromatograferes over kiselgel med kloroform/metanol (9:1). Utbytte: 0,3 g (90%), R r= 0,50 i kloroform/metanol (9:1). ;""■H-NMR (250 MHz, DMSO-dg i ppm) forbindelse (9): 7,5 (d, ;1H, NH, J=8,7 Hz); 5,52 (m, 1H, -CH2-CH=C); 5,35 (dd, 1H, C=CH-, J = 15,2 Hz, J = 6,5 Hz); 5,03 (d, 1H, OH, J = 3,4 Hz); ;4,92 (m, 3H, OH); 4,5 (t, 1H, OH, J = 4,9 Hz); 4,09 (d, 1H, H-l, J = 7,6 Hz); 4,0-3,55 (m, 4H); 3,45 (m, 2H); 3,15- ;2,9 (m, 4H); 2,1-1,88 (m, 4H); 1,45 (m, 2H); 1,22 (m, 54H, alifat.); 0,85 (m, 6H, CH3). ;Tillegg ;For å bekrefte den strukturen som er tilskrevet forbindelsen ;av formel (VI) er forbindelsen (4) underkastet den samme behand-lingen med hydrogensulfid (se nedenfor) som er beskrevet i avsnitt (h) i eksemplet ovenfor. Derved oppnådde man også virkelig forbindelsen (5), hvis fysikalsk-kjemiske egenskaper stemmer fullstendig overens med de for erythro-D-C^g-sphingo- ;sin fremstilt fra naturlige kilder. ;2S, 3R- 2- amino- l, 3- dihydroksy- 4- trans- eikosen (5) ;0,25 g (0,7 mmol) av forbindelse (4) oppløses i en blanding av 5 ml pyridin og 2 ml vann. Oppløsningen mettes med hydrogensulfid. Det omrøres; i. 48 timer ved ■romtemperatur,. Det inndampes.; til tørrhet. Resten kromatograferes bvér kiselgel, først med ' kloroform, så med kloroform/metanol (9:1) og til sist med kloroform/metanol/vann (8:2:0,25). Utbytte: 0,215 g (95%), ;Rp=0,2 i kloroform/metanol (1:1), smeltepunkt 70-72°C. ;""■H-NMR (250 MHz, CDC13 i ppm) forbindelse (5): 5,78 (m, 1H, ;-CH2-CH-C), 5,47 (dd, 1H, -CH2-CH=CH-, J = 15,5 Hz, J = 7,3 Hz); 4,12 (dd, 1H, C=CH-CH-OH, J = 6,1 Hz); 3,7 (m, 2H, CH2~OH); 2,93 (m, 1H, -CH-NH2); 2,57 (m, 4H, NH2, OH); 2,06 (m, 2H, C=CH-CH2); 1,45-1,18 (m, 26H, alifat.); 0,88 (t, 3H, -CH3). Eksempel 2 2S, 3R- 2- heksadekanoylamino- 3- hydroksy- l-( B- D- glukopyranosyl)-oksy)- 4- trans- oktadecen j ) 2R, 3R- 1, 3- O- benzyliden- 2- hydroksy- 4- trans- oktadecen (10) 70 g (0,13 mol) tetradecyltrifenylfosfoniumbromid suspen-deres under nitrogen i ca. 1 liter vannfri toluen mettet med nitrogen. Fenyllitium, som er fremstilt fra 6,5 g (0,94 mol) litium og 74 g (0,47 mol) brombenzen i ca. 200 ml vannfri eter, tilsettes uten ytterligere rensing dråpevis. Samtidig avkjøles blandingen til -15°C. Deretter tilsettes dråpevis 21,6 g (0,104 mol) 2,4-O-benzyliden-D-threose [se eksempel 1, forbindelse (1)] i ca. 150 ml vannfri tetrahydrofuran under nitrogen i løpet av 20 minutter. Etter ytterligere 20 minutter tilsettes først 150 ml metanol og deretter 250 ml vann. Det omrøres kraftig. Den organiske fasen inndampes etter fraskillelse av den vandige fasen. For rensing kromatografer es over kiselgel med petroleumseter/eddikester (9:1). Utbytte: 27 g (68%), R r=0,21 i petroleumseter/eddikester (9:1), smeltepunkt: 54-55°C. ;k) 2S, 3R- 2-azid o- l, 3-O-b enzylide n- 4- trans- oktadecen (11) ;10 g (0,025 mol) av forbindelse (10) oppløses i ca. 70 ml ;vannfri diklormetan som inneholder 5 ml vannfri pyridin. Det avkjøles under nitrogen til -15°C. 8,7 g (0,31 mol) trifluormetansulfonsyreanhydrid tilsettes langsomt dråpevis. Etter 15 minutter filtreres over kiselgel og elueres med diklormetan/petroleumseter (1:1). Blandingen spyles stadig med nitrogen. Det inndampes, og den tilbake-blivende oljen opptas i 150 ml vannfritt dimetylformamid. Under nitrogen tilsettes 7,5 g (0,1 mol) natriumazid. ;Det omrøres i 2 timer ved romtemperatur. Deretter fortynnes med ca. 350 ml diklormetan, filtreres og inndampes i vannstrålevakuum. For rensing kromatograferes over kiselgel med petroleumseter/eddikester (9:1). Utbytte: ;7,8 g (75%), R r=0,8 i petroleumseter/eddikester (9:1). ;1) 2S, 3R- 2- azido- l, 3- dihydroksy- 4- trans- oktadefcen (12) ;7 g (0,017 mol) av forbindelse (11) oppløses i 100 ml ;diklormetan. Det tilsettes 5 ml konsentrert saltsyre og ;3 ml vann og omrøres kraftig ved romtemperatur i 12 timer. ;Deretter utristes med vandig natriumhydrogenkarbonat-oppløsning. Den organiske fasen fraskilles, tørkes over natriumsulfat og inndampes. For rensing kromatograferes over kiselgel med diklormetan/metanol ( 95 : 5 ) . Utbytte: ;3,76 g (68%), R r=0,46 i diklormetan/metanol (95:5). ;<1>H-NMR (250 MHz, CDC13 i ppm): forbindelse (12): 5,83 (m, 1H, CH2-CH=C): 5,55 (dd, 1H, -CH2-CH=CH-, J = 15,5 Hz, ;J = 6,5 Hz)';- 4,25 (m, 1H, -CH-N3) ; 3,8 (m, 2H, -CH2-OH, )CH-OH) ,- 3V52 Cm., 1H, -CH2~OH); 2,05 (m, 4H, OH, C=CH-CH2) ; ;1,45-1,18 (m, 22H, alifat.); 0,88 (t, 3H, CH3). ;m) 2S, 3R- 2- azido- 3- hydroksy- l- Q- trifenylmetyl- 4- transoktadecen ;(13) 4 g (12,3 mmol) av forbindelse (12) oppløses i 45 ml av en blanding av vannfri pyridin/kloroform/tetrahydrofuran (1:1:1).- 6 g (21,5 mmol ) .tritylklor id tilsettes... Blandingen omrøres i 48 timer ved romtemperatur. Deretter inndampes i vannstrålevakuum. Resten opptas i 200 ml dietyleter og utristes med 100 ml vann. Den organiske fasen tørkes over magnesiumsulfat og inndampes. For rensing kromatograferes over kiselgel med petroleumseter/eddikester (9:1). Utbytte: 6.3 g (90%), R r=0,39 i petroleumseter/eddikester (9:1). ;<1>H-NMR (250 MHz, CDC13 i ppm) forbindelse (13): 7,55-7,15 (m, 15H, aromat.); 5,75-5,58 (m, 1H, CH2-CH=C); 5,38-5,26 (dd, 1H, CH2-CH=CH-, J = 15,5 Hz, J = 7,3 Hz); 4,20 (m, 1H, ;-CH-N3); 3,53 (m, 1H, -CH-OH); 3,30 (d, 2H, 0-CH2-, J = ;5.4 Hz); 2,03-1,188 (m, 3H, -OH, CH=CH-CH2); 1,40-1,10 (m, 22H, alifat.); 0,88 (t, 3H, CH3). ;2S, 3R- 2- azido- 3- benzoyloksy- l- 0- trifenylmetyl- 4- transoktadecen (14) ;6,3 g (11,1 mmol) av forbindelse (13) oppløses i 30 ml av en blanding av vannfri toluen/pyridin (4:1). 3 g (21,3mmol ) benzoylklorid tilsettes. Det omrøres i 12 timer ved romtemperatur. Deretter helles blandingen på 200 ml vann og ekstraheres 2 ganger, hver gang med 100 ml dietyleter. ;Den organiske fasen tørkes over magnesiumsulfat og inndampes. For rensing kromatograferes over kiselgel med petroleumseter/eddikester (95:5). Utbytte: 6,7 g (90%), R r=0,60 i petroleumseter/eddikester (9:1). ;2S, 3R- 2- a z i do- 3- ben zoy lok sy- 1- hyd r ok sy- 4- tr ans-. oktadecen (15) 6,7 g (9,97 mmol) av forbindelse (14) oppløses i en blanding av 30 ml vannfri toluen og 5 ml vannfri metanol. 10 ml 3M bortrifluorideterat i diklormetan tilsettes. Etter 5 timer helles blandingen på 50 ml is og den organiske fasen fraskilles. Etter tørking over magnesiumsulfat inndampes og det kromatograferes deretter først med petroleumseter/ eddikester (9:1), deretter med petroleumseter/eddikester (8:2). Utbytte: 3,8 (90%), R r=0,13 i petroleumseter/ eddikester (9:1). ;Elementæranalyse for C25H39<N>3°3 (Molekylvekt 429,56) Beregnet: C 69,90 H 9,14 N 9,78 ;Funnet: 69,92 9,16 9,65 ;<1>H-NMR (250 MHz, CDC13 i ppm) forbindelse (15): 8,14 ;(m, 2H, aromat.); 7,58 (m, 1H, aromat.); 7,47 (m, 2H, aromat.); 6,05-5,87 (m, 1H, CH2-CH-=C); 5,69-5,53 (m, ;2H, CH2-CH=CH-, CH-OBz); 2,15-1,95 (m, 3H, -OH, C=CH-CH2); 1,47-1,13 (m, 22H, alifat.); 0,86 (t, 3H, CH3). ;2S, 3R- 2- azido- 3- benzyloksy- l-( 2, 3, 4, 6- tetra- O- pivaloyl-8- D- glukopyranosyloksy)- 4- trans- oktadecen (16) ;2 g (4,6 mmol) av forbindelse (15) og 4,6 g (7,0 mmol) 2,3,4,6-tetra-O-pivaloyl-a-D-glukopyranosyltrikloracetimidat oppløses i 40 ml vannfri diklormetan og omrøres i 30 minutter med molekylarsikt 4 Å. Deretter tilsettes 0,2 ml 0,1M bortrif luorid-eterat i diklormetan. Under forløpet av reaksjonen til- ;settes, ytterligere 2 ml 0,1 M bor tr if luorat i porsjoner<*> The introduction of the protecting group R" takes place by the methods known in organic chemistry, corresponding to the type of the selected protecting group. For example, the triphenylmethyl group can be introduced by treating the ceramide with a corresponding halide such as triphenylchloromethane or triphenylbromomethane. Also for: tert.butyldimethylsilyl - and the tert.butyldiphenylsilyl group, the corresponding nalogenide, for example the chloride or bromide is advantageously used. Then the protected compound of formula (VIII) in the 1-position is protected by the hydroxyl group in the 3-position with a protective rses group R"', e.g. by esterification with an organic carboxylic acid Ac'OH or a reactive functional derivative thereof. Above all, simple, aliphatic carboxylic acids and aromatic, especially monocyclic aromatic carboxylic acids are suitable for this purpose. ;. preferred is the use of benzoic acid, a substituted benzoic acid or pivalic acid. The esterification with the carboxylic acid Ac'OH can be carried out by the methods described in "Ullmann's Encyklopadie der technischen Chemie", 4th edition, volume 11, page 91, Verlag Chemie GmbH, 5Weinheim BRD' (1976). It advantageously takes place using a carboxylic acid halide in the presence of a tertiary organic base such as triethylamine, pyridine or dimethylaniline, in an anhydrous organic solvent such as benzene, toluene, tetrahydrofuran, diethyl ether or dichloromethane. The protecting group R" on the hydroxyl group in the 1-position in the compound of formula (IX) can be cleaved off by acid hydrolysis (triphenylmethyl protecting groups, silyl protecting groups) or by treatment with boron trifluoride etherate (triphenylmethyl groups). The compound of formula (x) is obtained in which the hydroxyl group in the 3-position is blocked by the protecting group k"<1>, but the primary hydroxyl group in the 1-position is again free. ;The reaction of the compound (IX) or the compound (VI) with the O-trichloro- or O-trifluoro-acetimidate of a D-glucose, whose hydroxyl groups in addition to that at the 1-position are protected by means of acyl residues Ac, is advantageously catalyzed by means of a Lewis acid such as boron trifluoride etherate or trifluoromethane sulfonic acid trimethylsilyl ester. It is generally carried out in an anhydrous organic solvent such as a hydrocarbon (hexane) or a halogenated hydrocarbon (dichloromethane). Lower aliphatic acyl groups such as acetyl, propionyl, pivaloyl, trifluoroacetyl or methanesulfonyl groups are preferably used as acyl residues to protect the hydroxyl groups in the 2-, 3-, 4- and 6-positions in D-glucose. Details regarding the preparation of the reagent can be found in the thesis of R.R. Schmidt and M. Stumpp (Liebig's Ann. Chem. 1983, 1249-1256) and R.R. Schmidt, J. Michel and M. Roos (Liebig's Ann. Chem. 1984, 1343-1357). The corresponding reaction with the 1-halogen derivative of the O-tetraacylated D-glucose, for example with O-acetyl-α-D-glucopyranosyl chloride or bromide (the latter also referred to as α-D-O-acetobromoglucose), is usually carried out in the presence of a heavy metal compound such as silver oxide, a heavy metal salt , such as silver carbonate or mercuric cyanide, or an organic base, ;which acts as an acid-binding agent ("Ullmann's Encyklopadie der technischen Chemie", 4th edition, volume 24, page 757, Verlag Chemie GmbH, Weinheim BRD 1983). ;The cleavage of the acyl residues Ac and the protective group R"<1>; from the compound (VII) or (XI) is generally catalyzed by means of bases; particularly suitable for this purpose is the use of sodium methanolate in anhydrous methanol at room temperature. ;In the penultimate process step, the transfer of the azido group is provided to the primary amino group best by treating the compound (XII with hydrogen sulphide at room temperature. For this purpose the compound is dissolved for example in a mixture (1:1) of water and pyridine. This transfer can also be carried out by hydrogenation with sodium borohydride or with another reducing agent, such as e.g. sodium cyanoborohydride. The N-acylation of compound (XIII) with d! e.n organic carboxylic acid of the formula R -OH (last 1 £iemg;ang;s.method.rinni> Icara is carried out by the method according to D. Shapiro and; ;collaborators [J. Am. Chem. Soc. 86, 4472 (1964) ]. In general, the carboxylic acid itself is used in the presence of a water splitting agent, such as dicyclohexylcarbodiimide in dichloromethane, or a functionally reactive derivative of the carboxylic acid, such as an activated ester or a halide in the presence of an inorganic base such as sodium acetate or a tertiary organic base. N- the acylation is advantageously carried out at room temperature. The isolation and purification of the compounds that occur in each process takes place by known methods in organic chemistry. The following examples illustrate preferred embodiments of the invention. <1>H-NMR spectra were measured with the 250 MHz instrument "WM 250 Cryospec" for the company Bruker, Spectrospin, Industriestrasse 26, CH-8117 Fallanden/ziirich. The displacements are given on the basis of tetramethylsilane (TMS) as internal standard and stated in ppm. ;The stated melting points are determined on a copper block and are ;not corrected. For analytical thin-layer chromatography (DC), silica gel plates from the company E. Merck AG, Darmstadt, (BRD) were used. The thin-layer chromatograms were, as long as the substances were not UV-active, sprayed with 15% sulfuric acid and developed at 120°C. ;Preparative column chromatography was carried out with "Kieselgel 60" ;(0.062-0.200 mm) from the company Merck. For intermediate pressure chromatography, ready-made columns were used according to D. Flockerzi, Diplomarbeit, Universitat Stuttgart/BRD (1978), with silica gel "LiChroprep Si;60, 15-25". ;The yields were indicated at the purification step where no impurities could be detected anymore by NMR spectroscopically and by means of thin-layer chromatography. ;i ;For the solvent mixtures, the indications in brackets mean ;parts by volume. ; Example 1 ; 2S, 3R- 2- hexadecanoylamino- 3- hydroxy- 1-( B- D- glucopyranosyloxy)- i ; 4- trans- eicosene ; a) 4, 6- 0- benzylidene- D- galactose ; See J Org. Che. 29, 3647-3654 (1964). ;D ;b) 2,4-O-benzylidene-D-threose (1) ;30 g (0.111 mol) 4,6-O-benzylidene-D-galactose is dissolved in ;approx. 1,200 ml phosphate buffer of pH 7.6. 55 g (0.257 mol) of sodium periodate are added with vigorous stirring. The pH-5 value is maintained by the dropwise addition of 2N caustic soda at approx. ;7 to 8. It is stirred for 1.5 hours at room temperature. It is then evaporated to dryness in a water jet vacuum. The solid residue is extracted 4 times, each time with 250 ml of vinegar. The extract is filtered, dried over magnesium sulfate and evaporated. Yield: 20 g (85%), Rp=0.64 in toluene/ethanol (3:1). ;c) 2S,3R-1,3-0-benzylidene-2-hydroxy-4-trans-eicose (2) 70 g (0.12 mol) of hexadecyltriphenylphosphonium bromide are suspended under nitrogen for approx. 1 liter anhydrous toluene saturated with nitrogen. Phenyllithium, prepared from 6.5 g (0.94 mol) lithium and 74 g (0.47 mol) bromobenzene in approx. 200 ml of anhydrous ether is added dropwise without further purification. At the same time, the mixture is cooled to -15°C. 20 g (0.096 mol) of compound (1) are then added dropwise in approx. 150 ml anhydrous tetrahydrofuran under nitrogen during 20 minutes. After a further 20 minutes, first 150 ml of methanol and then 250 ml are added. water. It is stirred vigorously. The organic phase is evaporated after separation of the aqueous phase. ;For purification, chromatograph over silica gel with petroleum ether/acetic ester (9:1). Yield 27 g (68%), R r=0.21 in petroleum ether/acetic ester (9:1). ;d) 2S,3R-2-Azido—1,3-0-benzylidene-4-trans-eicose (3); 10 g (0.025 mol) of the compound (2) are dissolved in approx. 70 ml of anhydrous dichloromethane, which contains 5 ml of anhydrous pyridine. It is cooled under nitrogen to -15°C. 8.12 g (0.029 mol) of trifluoromethanesulfonic acid are added slowly and dropwise. After 15 mi the nut is filtered; over silica gel and elute with dikloone.tan/pe.tr.oleumseter (1:1);. The mixture is constantly flushed; with. nitrogen. The. is evaporated and the residual oil" is absorbed; in 50 ml of anhydrous dimethylformamide. Underneath, nitrogen is added. 7.5 g (0.1 mol) sodium azide. The mixture is stirred for 2 hours at room temperature. It is then diluted with approx. 350 ml of dichloromethane, filtered and evaporated in a water jet vacuum. For purification, chromatograph over silica gel with petroleum ether/acetic ester (9:1). Yield: 8 g (75%), R.p=0.8 in petroleum ether/acetic ester (9:1). ;e) 2S,3R-2-azido-1,3-dihydroxy-4-trans-eicosene (4) 8 g (0.018 mol) of compound (3) are dissolved in 100 ml of dichloromethane. 5 ml of concentrated hydrochloric acid and 3 ml of water are added and stirred vigorously at room temperature for 12 hours. Then shake out with aqueous sodium hydrogencarbonate solution. The organic phase is separated, dried over sodium sulphate and evaporated. For purification, chromatograph over silica gel with dichloromethane/methanol (95:5) .. Yield: 4.32 g (68%), R r=0.46 in dichloromethane/inethanol (95:5), melting point 56-57°C . ;Elementary analysis: calculated C 67.95 H 11.11 N 11.88 ;found 67.62 11.12 11.85 ;<1>H-NMR (250 MHz, CDC13 in ppm) compound (4): 5.83 (m, 1H, -CH2-CH=C); 5.55 (dd, 1H, -CH2-CH=CH-, J = 15.5 Hz, ;J = 6.5 Hz); 4.25 (m, 1H, -CH-N3); 3.8 (m, 2H, -CH_2-OH, CH-OH); 3.52 (m, 1H, -CH 2 -OH); 2.05 (m, 4H, OH, C=CH-CH2 ) ; ;1.45-1.18 (m, 26H, aliphat.); 0.88 (t, 3H, CH3) . ;f) 2S, 3R- 2- azido- 2- hydroxy- 1-(2, 3, 4, 6- tetra- O- acetyl- B-D- qlucopyranosyloxy_) - 4- trans- eicosene ( 6 ) ; 0.5 g (1.41 mmol) of compound (4) is dissolved in 50 ml of anhydrous hexane. 0.1 ml of 0.5 M boron trifluoride etherate in dichloromethane and a spatula tip molecular sieve 4 Å are added. 0.7 g (1.41 mmol) O-(2,3,4,6-tetra-O-acetyl-a-D- gluco-pyranosyl)-trichloroacetimidate is dissolved in 3 ml of anhydrous toluene and added slowly drop by drop. After 4 hours, wash with 30 ml saturated sodium bicarbonate solution. The aqueous phase is decanted 3 times, each time with 30 ml of dichloromethane. The organic phases are dried over sodium sulfate and evaporated. For purification, chromatograph over silica gel with dichloromethane/methanol (97.5:2.5). Yield: 0.385 g (40%), Rp=0.7 in dichloromethane/methanol (95:5). ;<1>H-NMR (250 MHz, CDCl 3 in ppm) compound (6): 5.78 (m, 1H, -CH 2 -CH=C); 5.5 (dd, lfl, -Cri 2 -CH=CH, J = 15.5 Hz, J = 7.3 Hz); 5.3-4.98 (m, 3H, H-2, H-3, H-4); 4.58 (d, 1H, H-1, ; J = 7.6 Hz); 4.35-4.13 (m, 3H, H-6, H-6; -CH-N3); 4.05 (dd, 1H, -CH2-O-); 3.73 (m, 2H, H-5, -CH2~O); 3.47 (m, 1H, ; ;CH-OH); 2.24 (d, 1H, OH, J = 4.8 Hz); 2.16-1.94 (m, 14H, acetyl, C=CH-CH_2); 1.45-1.15 (m, 26H, aliphat.); 0.88 (t, 3H, -Cl 3 ). ;g ) 2S„- 3R- 2- azido- 3- hydroxy- 1-(B- D- glucopyranosyloxy)- 4-trans-eicose (7) ; 0.4 g (0.585 mmol) of compound (6) is dissolved in 30 ml anhydrous methanol. 0.2 ml of an IM solution of sodium methylate in methanol is added. It is stirred for 1 hour at room temperature. It is then neutralized with the ion exchanger "Amberlite IR 120" (H+<->form). The ion exchanger is filtered off, it is evaporated and chromatographed over silica gel with chloroform/methanol (9:1). Yield: 0.26 g (86%), R = 0.22 in chloroform/methanol (9:1). ;<1>H-NMR (250 MHz, DMSO-d6 in ppm) compound (7): 4.10 (d, 1H, H-1, J=7.6 Hz). ;h) 2S, 3R- 2- amino- 3- hydroxy- 1-(B- D- glucopyranosyloxy)- 4-trans-eicose (8) ; 0.26 g (0.5 mmol) of compound (7) is dissolved in a mixture of 4 ml pyridine and 4 ml water. The solution is saturated with hydrogen sulphide. It is stirred for 24 hours at room temperature. It is evaporated to dryness and chromatographed over silica gel first with chloroform/methanol (6:4), then with chloroform/methanol/water (5:4:1). Yield: 0.234 g (96%), R r=0.65 in chloroform/methanol/water (5:4::1). ;^H-NMR (250 MHz,;DMSO-d 6 in ppm) compound (8): 4.10 ;(d, IK, H-1, J = 7.6 Hz). ;i) 2S,3R-2-hexadecanoylamino-3-hydroxy-1-(8-D^glucopyrano-sy1oxy)-4- trans-eicose (9) ;0.23 g (0.47 mmol) of compound (8 ) is dissolved in 5 ml of tetrahydrofuran. 5 ml of a 50% aqueous sodium acetate solution is added. The mixture is mixed at room temperature with vigorous stirring with 0.19 g (0.7 mmol) of hexadecanoyl chloride. After approx. After 2 hours, the organic phase is separated. The aqueous phase is decanted 3 times, each time with 2 ml of chloroform. The organic phase is dried over sodium sulfate and evaporated. For purification, chromatograph over silica gel with chloroform/methanol (9:1). Yield: 0.3 g (90%), R r= 0.50 in chloroform/methanol (9:1). ;"" H-NMR (250 MHz, DMSO-dg in ppm) compound (9): 7.5 (d, ;1H, NH, J=8.7 Hz); 5.52 (m, 1H, -CH 2 -CH=C); 5.35 (dd, 1H, C=CH-, J = 15.2 Hz, J = 6.5 Hz); 5.03 (d, 1H, OH, J = 3.4 Hz); ; 4.92 (m, 3H, OH); 4.5 (t, 1H, OH, J = 4.9 Hz); 4.09 (d, 1H, H-1, J = 7.6 Hz); 4.0-3.55 (m, 4H); 3.45 (m, 2H); 3.15- ;2.9 (m, 4H); 2.1-1.88 (m, 4H); 1.45 (m, 2H); 1.22 (m, 54H, aliphat.); 0.85 (m, 6H, CH3). Addendum To confirm the structure attributed to the compound of formula (VI), compound (4) is subjected to the same treatment with hydrogen sulfide (see below) as described in paragraph (h) of the above example. Thereby, the compound (5) was indeed obtained, whose physico-chemical properties correspond completely to those of erythro-D-C^g-sphingosine prepared from natural sources. ;2S,3R-2-amino-1,3-dihydroxy-4-trans-eicose (5) ;0.25 g (0.7 mmol) of compound (4) is dissolved in a mixture of 5 ml pyridine and 2 ml water. The solution is saturated with hydrogen sulphide. It is stirred; in. 48 hours at room temperature,. It evaporates.; to dryness. The residue is chromatographed either on silica gel, first with chloroform, then with chloroform/methanol (9:1) and finally with chloroform/methanol/water (8:2:0.25). Yield: 0.215 g (95%), ;Rp=0.2 in chloroform/methanol (1:1), melting point 70-72°C. ;"" H-NMR (250 MHz, CDCl3 in ppm) compound (5): 5.78 (m, 1H, ;-CH2-CH-C), 5.47 (dd, 1H, -CH2-CH=CH -, J = 15.5 Hz, J = 7.3 Hz); 4.12 (dd, 1H, C=CH-CH-OH, J = 6.1 Hz); 3.7 (m, 2H, CH2~OH); 2.93 (m, 1H, -CH-NH 2 ); 2.57 (m, 4H, NH 2 , OH); 2.06 (m, 2H, C=CH-CH 2 ); 1.45-1.18 (m, 26H, aliphat.); 0.88 (t, 3H, -CH 3 ). Example 2 2S,3R-2-hexadecanoylamino-3-hydroxy-1-(B-D-glucopyranosyl)-oxy)-4-trans-octadecenej) 2R,3R-1,3-O-benzylidene-2-hydroxy- 4-trans-octadecene (10) 70 g (0.13 mol) of tetradecyltriphenylphosphonium bromide are suspended under nitrogen for approx. 1 liter anhydrous toluene saturated with nitrogen. Phenyllithium, which is prepared from 6.5 g (0.94 mol) lithium and 74 g (0.47 mol) bromobenzene in approx. 200 ml of anhydrous ether is added dropwise without further purification. At the same time, the mixture is cooled to -15°C. 21.6 g (0.104 mol) of 2,4-O-benzylidene-D-threose [see example 1, compound (1)] are then added dropwise in approx. 150 ml anhydrous tetrahydrofuran under nitrogen during 20 minutes. After a further 20 minutes, first 150 ml of methanol and then 250 ml of water are added. It is stirred vigorously. The organic phase is evaporated after separation of the aqueous phase. For purification, the chromatograph is over silica gel with petroleum ether/acetic ester (9:1). Yield: 27 g (68%), R r=0.21 in petroleum ether/acetic ester (9:1), melting point: 54-55°C. ;k) 2S, 3R- 2-azide o- 1, 3-O-b enzylide n- 4- trans- octadecene (11) ; 10 g (0.025 mol) of compound (10) are dissolved in approx. 70 ml of anhydrous dichloromethane containing 5 ml of anhydrous pyridine. It is cooled under nitrogen to -15°C. 8.7 g (0.31 mol) of trifluoromethanesulfonic anhydride are slowly added dropwise. After 15 minutes, filter over silica gel and elute with dichloromethane/petroleum ether (1:1). The mixture is constantly flushed with nitrogen. It is evaporated, and the remaining oil is taken up in 150 ml of anhydrous dimethylformamide. Under nitrogen, 7.5 g (0.1 mol) of sodium azide are added. It is stirred for 2 hours at room temperature. Then dilute with approx. 350 ml of dichloromethane, filtered and evaporated in a water jet vacuum. For purification, chromatograph over silica gel with petroleum ether/acetic ester (9:1). Yield: 7.8 g (75%), R r=0.8 in petroleum ether/acetic ester (9:1). ;1) 2S,3R-2-azido-1,3-dihydroxy-4-trans-octadefcene (12) 7 g (0.017 mol) of compound (11) are dissolved in 100 ml of dichloromethane. 5 ml of concentrated hydrochloric acid and 3 ml of water are added and stirred vigorously at room temperature for 12 hours. ;Then shake out with aqueous sodium bicarbonate solution. The organic phase is separated, dried over sodium sulphate and evaporated. For purification, chromatograph over silica gel with dichloromethane/methanol (95:5). Yield: 3.76 g (68%), R r=0.46 in dichloromethane/methanol (95:5). ;<1>H-NMR (250 MHz, CDCl3 in ppm): compound (12): 5.83 (m, 1H, CH2-CH=C): 5.55 (dd, 1H, -CH2-CH=CH -, J = 15.5 Hz, ;J = 6.5 Hz)';- 4.25 (m, 1H, -CH-N3) ; 3.8 (m, 2H, -CH2-OH, )CH-OH) ,- 3V52 Cm., 1H, -CH2~OH); 2.05 (m, 4H, OH, C=CH-CH 2 ); ;1.45-1.18 (m, 22H, aliphat.); 0.88 (t, 3H, CH3). ;m) 2S, 3R- 2- azido- 3- hydroxy- l- Q- triphenylmethyl- 4- transoctadecene ; (13) 4 g (12.3 mmol) of compound (12) are dissolved in 45 ml of a mixture of anhydrous pyridine/chloroform/tetrahydrofuran (1:1:1).- 6 g (21.5 mmol) of trityl chloride are added... The mixture is stirred for 48 hours at room temperature. It is then evaporated in a water jet vacuum. The residue is taken up in 200 ml of diethyl ether and shaken out with 100 ml of water. The organic phase is dried over magnesium sulfate and evaporated. For purification, chromatograph over silica gel with petroleum ether/acetic ester (9:1). Yield: 6.3 g (90%), R r=0.39 in petroleum ether/acetic ester (9:1). ;<1>H-NMR (250 MHz, CDCl3 in ppm) compound (13): 7.55-7.15 (m, 15H, arom.); 5.75-5.58 (m, 1H, CH2-CH=C); 5.38-5.26 (dd, 1H, CH2-CH=CH-, J = 15.5 Hz, J = 7.3 Hz); 4.20 (m, 1H, ;-CH-N3); 3.53 (m, 1H, -CH-OH); 3.30 (d, 2H, O-CH2-, J = ;5.4 Hz); 2.03-1.188 (m, 3H, -OH, CH=CH-CH2); 1.40-1.10 (m, 22H, aliphat.); 0.88 (t, 3H, CH3). ; 2S, 3R- 2- azido- 3- benzoyloxy-l- 0- triphenylmethyl- 4- transoctadecene (14) ; 6.3 g (11.1 mmol) of compound (13) are dissolved in 30 ml of a mixture of anhydrous toluene/pyridine (4:1). 3 g (21.3 mmol) of benzoyl chloride are added. It is stirred for 12 hours at room temperature. The mixture is then poured into 200 ml of water and extracted twice, each time with 100 ml of diethyl ether. The organic phase is dried over magnesium sulphate and evaporated. For purification, chromatograph over silica gel with petroleum ether/acetic ester (95:5). Yield: 6.7 g (90%), R r=0.60 in petroleum ether/acetic ester (9:1). ;2S, 3R- 2- a z i do- 3- ben zoy lok sy- 1- hyd r ok sy- 4- tr ans-. octadecene (15) 6.7 g (9.97 mmol) of compound (14) are dissolved in a mixture of 30 ml anhydrous toluene and 5 ml anhydrous methanol. 10 ml of 3M boron trifluoride etherate in dichloromethane is added. After 5 hours, the mixture is poured onto 50 ml of ice and the organic phase is separated. After drying over magnesium sulphate, it is evaporated and it is then chromatographed first with petroleum ether/acetic ester (9:1), then with petroleum ether/acetic ester (8:2). Yield: 3.8 (90%), R r=0.13 in petroleum ether/acetic acid (9:1). ;Elementary analysis for C25H39<N>3°3 (Molecular weight 429.56) Calculated: C 69.90 H 9.14 N 9.78 ;Found: 69.92 9.16 9.65 ;<1>H-NMR ( 250 MHz, CDCl 3 in ppm) compound (15): 8.14 ;(m, 2H, arom.); 7.58 (m, 1H, arom.); 7.47 (m, 2H, arom.); 6.05-5.87 (m, 1H, CH2-CH-=C); 5.69-5.53 (m, ;2H, CH2-CH=CH-, CH-OBz); 2.15-1.95 (m, 3H, -OH, C=CH-CH2); 1.47-1.13 (m, 22H, aliphat.); 0.86 (t, 3H, CH3). ; 2S, 3R- 2- azido- 3- benzyloxy- 1-(2, 3, 4, 6- tetra- O- pivaloyl-8- D- glucopyranosyloxy)- 4- trans- octadecene (16) ; 2 g (4 .6 mmol) of compound (15) and 4.6 g (7.0 mmol) of 2,3,4,6-tetra-O-pivaloyl-α-D-glucopyranosyltrichloroacetimidate are dissolved in 40 ml of anhydrous dichloromethane and stirred for 30 minutes with a molecular sieve 4 Å. Then 0.2 ml of 0.1 M boron trifluoride etherate in dichloromethane is added. During the course of the reaction, a further 2 ml of 0.1 M boron trifluoride are added in portions<*>
på 0,5 ml. Etter 48 timer fortynnes med 200 ml petroleums- of 0.5 ml. After 48 hours, dilute with 200 ml of petroleum
eter og frafiltreres. Filtratet utristes med 50 ml vann- ether and filtered off. The filtrate is shaken out with 50 ml of water
fri natriumhydrogenkarbonatoppløsning, den organiske fasen tørkes over natriumsulfat og inndampes. For rensing kromatograferes over kiselgel med toluen/aceton (97,5:2,5). free sodium bicarbonate solution, the organic phase is dried over sodium sulfate and evaporated. For purification, chromatograph over silica gel with toluene/acetone (97.5:2.5).
Utbytte: 4 g (94%), R r=0,57 i toluen/aceton (97,5:2,5). Yield: 4 g (94%), R r=0.57 in toluene/acetone (97.5:2.5).
<1>H-NMR (250 MHz, CDC13 i ppm) forbindelse (16): 8,5 <1>H-NMR (250 MHz, CDCl3 in ppm) compound (16): 8.5
(m, 2H, aromat.); 7,58 (m, 1H, aromat.); 7,45 (m, 2H, (m, 2H, arom.); 7.58 (m, 1H, arom.); 7.45 (m, 2H,
aromat.); 5,99-5,83 (m, 1H, CH2-CH=C); 5,65-5,46 (m, 2H, aromat.); 5.99-5.83 (m, 1H, CH2-CH=C); 5.65-5.46 (m, 2H,
CH2-CH=CH, CH-OBz); 5,37-5,02 (m, 3H, H-2, H-3, H-4); 4,58 CH2-CH=CH, CH-OBz); 5.37-5.02 (m, 3H, H-2, H-3, H-4); 4.58
(d, 1H, H-l, 1 = 7,9 Hz); 4,25-3,58 (m, 6H, H-6, H-6', H-5, CH-N3, CH2-0); 2,06 (m, 2.H, CH=CH-CH2); 1,45-1,04 (d, 1H, H-1, 1 = 7.9 Hz); 4.25-3.58 (m, 6H, H-6, H-6', H-5, CH-N3, CH2-O); 2.06 (m, 2.H, CH=CH-CH2); 1.45-1.04
(in, 58H, pivaloyl, alifat. ) ; 0,89 (t, 3K, CH3). (in, 58H, pivaloyl, aliphat. ) ; 0.89 (t, 3K, CH 3 ).
2S, 3R- 2- azido- 3- hydroksy- l-( B- D- glukqpyranosyloksy)- 4-trans- oktadecen (17) 4 g (4,3 mmol") av forbindelse (16) oppløses i 50 ml vannfri diklormetan. 8 ml av en 0,05 M natriummetylatoppløsning i vannfri metanol tilsettes. Det omrøres i 3 dager ved romtemperatur. Deretter nøytraliseres med ioneveksler "Amberlit JR 120" (H+<->form). Ioneveksleren frafiltreres, 2S, 3R-2-azido-3-hydroxyl-(B-D-gluqpyranosyloxy)-4-trans-octadecene (17) 4 g (4.3 mmol") of compound (16) are dissolved in 50 ml of anhydrous dichloromethane . 8 ml of a 0.05 M sodium methylate solution in anhydrous methanol is added. It is stirred for 3 days at room temperature. Then neutralized with ion exchanger "Amberlit JR 120" (H+<-> form). The ion exchanger is filtered off,
det inndampes og kromatograferes over kiselgel med kloroform/metanol (8,5:1,5). Utbytte: 1,65 g (78%), Rp=0,20it is evaporated and chromatographed over silica gel with chloroform/methanol (8.5:1.5). Yield: 1.65 g (78%), Rp=0.20
i kloroform/metanol (9:1). in chloroform/methanol (9:1).
<1>H-NMR (250 MHz, DMSO-dg i ppm) forbindelse (17): <1>H-NMR (250 MHz, DMSO-dg in ppm) compound (17):
4,10 (d, 1H, H-l, J = 7,6 Hz). 4.10 (d, 1H, H-1, J = 7.6 Hz).
r) 2S, 3R- 2- amino- 3- hydroksy- l- ( B- D- g3 ucopyranosyloksy ) - 4-trans- oktadecen (18) r) 2S, 3R- 2- amino- 3- hydroxy-l-( B- D- g3 ucopyranosyloxy ) - 4-trans- octadecene (18)
1,65 g (3,4 mmol ) av forbindelse (17) oppløses i 50 ml av blanding av pyridin/vann (1:1). Oppløsningen mettes med hydrogensulfid. Det omrøres i 24 timer ved romtemperatur. Det inndampes til tørrhet og kromatograferes over kiselgel, først med kloroform/metanol (9:1), deretter med kloroform/metanol/vann (5:4:1). 1.65 g (3.4 mmol) of compound (17) are dissolved in 50 ml of a mixture of pyridine/water (1:1). The solution is saturated with hydrogen sulphide. It is stirred for 24 hours at room temperature. It is evaporated to dryness and chromatographed over silica gel, first with chloroform/methanol (9:1), then with chloroform/methanol/water (5:4:1).
Utbytte: 1,47 g (94%), Rp=0,64 i kloroform/metanol/vann (5:4:1). Yield: 1.47 g (94%), Rp=0.64 in chloroform/methanol/water (5:4:1).
<1>H-NMR (250 MHz, DMSO-dg i ppm) forbindelse (18): <1>H-NMR (250 MHz, DMSO-dg in ppm) compound (18):
4,10 (d, 1H, H-l, J = 7,6 Hz). 4.10 (d, 1H, H-1, J = 7.6 Hz).
s) 2S, 3R- 2- heksadekanoylamino- 3- hydroksy- l-( e- D- gluc opyrano-syloksy )- 4- trans- oktadecen (19) s) 2S, 3R- 2- hexadecanoylamino- 3- hydroxy- 1-( e- D- glucopyrano-siloxy )- 4- trans- octadecene (19)
1,47 g (3,2mmol ) av forbindelse (18) oppløses i 50 ml tetrahydrofuran. 50 ml av en 50% vandig natriumacetat-oppløsning tilsettes. Blandingen blandes ved romtemperatur under kraftig omrøring med 0,87 g (3,2mmol ) heksadekanoyl-klorid. Etter ca. 2 timer fortynnes blandingen med 350 ml tetrahydrofuran og den vandige fasen fraskilles. Den 1.47 g (3.2 mmol) of compound (18) are dissolved in 50 ml of tetrahydrofuran. 50 ml of a 50% aqueous sodium acetate solution is added. The mixture is mixed at room temperature with vigorous stirring with 0.87 g (3.2 mmol) of hexadecanoyl chloride. After approx. After 2 hours, the mixture is diluted with 350 ml of tetrahydrofuran and the aqueous phase is separated. It
organiske fasen utristes 2 ganger, hver gang med 50 ml mettet koksaltoppløsning og inndampes. Resten tørkes i høyvakuum. For rensing kromatograferes over kiselgel, først med kloroform, deretter med kloroform/metanol (9:1). Utbytte: 1,81 g (81%), Rp = 0,4 i kloroform/metanol (8,5: 1,5). the organic phase is decanted twice, each time with 50 ml saturated sodium chloride solution and evaporated. The rest is dried in a high vacuum. For purification, chromatograph over silica gel, first with chloroform, then with chloroform/methanol (9:1). Yield: 1.81 g (81%), Rp = 0.4 in chloroform/methanol (8.5:1.5).
""■H-NMR ( 250 MHz, DMSO-d6 i ppm) forbindelse (19): 7,5 (d, 1H, NH, J = 8,7 Hz); 5,52 (m, 1H, -CH2-CH=C); 5,35 (dd, 1H, CH2-CH=CH-, J = 15,2 Hz, J = 6,5 Hz); 5,03 ""■H-NMR (250 MHz, DMSO-d6 in ppm) compound (19): 7.5 (d, 1H, NH, J = 8.7 Hz); 5.52 (m, 1H, -CH 2 -CH=C); 5.35 (dd, 1H, CH2-CH=CH-, J = 15.2 Hz, J = 6.5 Hz); 5.03
(d, 1H, OH, J = 3,4 Hz); 4,92 (m, 3ri, OH); 4,5 (t, 1H, OH, J = 4,9 Hz); 4,09 (d, 1H, H-l, J = 7,6 Hz); 4,0-3,55 (m, 4H); 3,45 (m, 2H); 3,15-2,9 (m, 4H); 2,1-1,88 (m, 4H); 1,45 (m, 2H); 1,22 (m, 50H, alifat.); 0,85 (t, 6H, CH3) . (d, 1H, OH, J = 3.4 Hz); 4.92 (m, 3ri, OH); 4.5 (t, 1H, OH, J = 4.9 Hz); 4.09 (d, 1H, H-1, J = 7.6 Hz); 4.0-3.55 (m, 4H); 3.45 (m, 2H); 3.15-2.9 (m, 4H); 2.1-1.88 (m, 4H); 1.45 (m, 2H); 1.22 (m, 50H, aliphat.); 0.85 (t, 6H, CH3) .
Claims (12)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH347285 | 1985-08-13 | ||
| CH93886 | 1986-03-07 |
Publications (4)
| Publication Number | Publication Date |
|---|---|
| NO863251D0 NO863251D0 (en) | 1986-08-12 |
| NO863251L NO863251L (en) | 1987-02-16 |
| NO163453B true NO163453B (en) | 1990-02-19 |
| NO163453C NO163453C (en) | 1990-05-30 |
Family
ID=25686169
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO863251A NO163453C (en) | 1985-08-13 | 1986-08-12 | PROCEDURE FOR THE PREPARATION OF SPHINGOSIN DERIVATIVES. |
Country Status (14)
| Country | Link |
|---|---|
| US (1) | US4937328A (en) |
| EP (1) | EP0212400B1 (en) |
| AR (1) | AR242395A1 (en) |
| AT (1) | ATE71104T1 (en) |
| AU (1) | AU603773B2 (en) |
| CA (1) | CA1267891A (en) |
| DE (1) | DE3683214D1 (en) |
| DK (1) | DK165984C (en) |
| ES (1) | ES2001208A6 (en) |
| FI (1) | FI82058C (en) |
| HU (1) | HU197916B (en) |
| NO (1) | NO163453C (en) |
| PL (1) | PL149578B1 (en) |
| YU (1) | YU142886A (en) |
Families Citing this family (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3819870A1 (en) * | 1987-06-12 | 1988-12-29 | Hoerrmann Wilhelm | Pharmaceuticals based on fatty amino alcohols |
| EP0299201A3 (en) * | 1987-06-12 | 1990-08-22 | Wilhelm Dr. Hoerrmann | Pharmaceutical composition containing a fatty amino-alcohol |
| IT1235162B (en) * | 1988-12-02 | 1992-06-22 | Fidia Farmaceutici | LYSOSPHINGOLIPID DERIVATIVES |
| FR2673179B1 (en) * | 1991-02-21 | 1993-06-11 | Oreal | CERAMIDES, THEIR PREPARATION PROCESS AND THEIR APPLICATIONS IN COSMETICS AND DERMOPHARMACY. |
| GB9207182D0 (en) * | 1992-04-01 | 1992-05-13 | Enzymatix Ltd | Glycolipids and their preparation |
| WO1994009020A1 (en) * | 1992-10-22 | 1994-04-28 | Kirin Beer Kabushiki Kaisha | Novel shingoglycolipid and use thereof |
| WO1995003028A1 (en) * | 1993-07-23 | 1995-02-02 | Morris Herstein | Cosmetic, skin-renewal stimulating composition with long-term irritation control |
| JP3783730B2 (en) * | 1993-10-18 | 2006-06-07 | バージニア テック インテレクチュアル プロパティーズ，インコーポレイティド | Synthesis of sphingosine |
| CA2142153A1 (en) * | 1994-03-04 | 1995-09-05 | Jacques Banville | Sulfated .beta.-glycolipid derivatives as cell adhesion inhibitors |
| US5663151A (en) * | 1994-03-04 | 1997-09-02 | Bristol-Myers Squibb Company | Sulfated α-glycolipid derivatives as cell adhesion inhibitors |
| US5686426A (en) * | 1994-11-17 | 1997-11-11 | Bristol-Myers Squibb Company | Dicarboxymethylated glycolipid derivatives as cell adhesion inhibitors |
| DE69914560T2 (en) | 1998-05-14 | 2004-12-23 | Cosmoferm B.V. | METHOD FOR ACYLATING AMINOALCOHOLS |
| DE60005513T2 (en) * | 1999-05-10 | 2004-07-15 | Lipiderm Ltd. | PROCESS FOR THE PRODUCTION OF SPHINGOSINS AND CERAMIDS IN A LARGE SCALE |
| US7156661B2 (en) * | 2002-08-22 | 2007-01-02 | Align Technology, Inc. | Systems and methods for treatment analysis by teeth matching |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2478104B1 (en) * | 1980-03-17 | 1986-08-08 | Merieux Inst | NEW GANGLIOSIDE DERIVATIVES, THEIR PREPARATION AND THEIR APPLICATION |
| EP0146810A3 (en) * | 1983-12-05 | 1987-05-13 | Solco Basel AG | Process for the preparation of sphingosin derivatives |
-
1986
- 1986-08-02 EP EP86110694A patent/EP0212400B1/en not_active Expired - Lifetime
- 1986-08-02 DE DE8686110694T patent/DE3683214D1/en not_active Expired - Fee Related
- 1986-08-02 AT AT86110694T patent/ATE71104T1/en not_active IP Right Cessation
- 1986-08-11 AR AR86304868A patent/AR242395A1/en active
- 1986-08-11 DK DK382486A patent/DK165984C/en not_active Application Discontinuation
- 1986-08-11 US US06/895,181 patent/US4937328A/en not_active Expired - Fee Related
- 1986-08-11 HU HU863523A patent/HU197916B/en not_active IP Right Cessation
- 1986-08-12 FI FI863272A patent/FI82058C/en not_active IP Right Cessation
- 1986-08-12 CA CA000515738A patent/CA1267891A/en not_active Expired - Fee Related
- 1986-08-12 AU AU61083/86A patent/AU603773B2/en not_active Ceased
- 1986-08-12 ES ES8601030A patent/ES2001208A6/en not_active Expired
- 1986-08-12 PL PL1986261011A patent/PL149578B1/en unknown
- 1986-08-12 YU YU01428/86A patent/YU142886A/en unknown
- 1986-08-12 NO NO863251A patent/NO163453C/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| ES2001208A6 (en) | 1988-05-01 |
| NO863251L (en) | 1987-02-16 |
| DK382486D0 (en) | 1986-08-11 |
| US4937328A (en) | 1990-06-26 |
| DE3683214D1 (en) | 1992-02-13 |
| DK165984C (en) | 1993-07-19 |
| AU603773B2 (en) | 1990-11-29 |
| EP0212400A3 (en) | 1987-10-28 |
| AR242395A1 (en) | 1993-03-31 |
| AU6108386A (en) | 1987-02-19 |
| FI863272A0 (en) | 1986-08-12 |
| FI82058B (en) | 1990-09-28 |
| HUT42500A (en) | 1987-07-28 |
| DK382486A (en) | 1987-02-14 |
| NO163453C (en) | 1990-05-30 |
| EP0212400A2 (en) | 1987-03-04 |
| HU197916B (en) | 1989-06-28 |
| NO863251D0 (en) | 1986-08-12 |
| PL149578B1 (en) | 1990-02-28 |
| PL261011A1 (en) | 1987-06-01 |
| FI82058C (en) | 1991-01-10 |
| CA1267891A (en) | 1990-04-17 |
| YU142886A (en) | 1988-06-30 |
| ATE71104T1 (en) | 1992-01-15 |
| EP0212400B1 (en) | 1992-01-02 |
| DK165984B (en) | 1993-02-22 |
| FI863272A (en) | 1987-02-14 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| NO163453B (en) | PROCEDURE FOR THE PREPARATION OF SPHINGOSIN DERIVATIVES. | |
| Mukaiyama et al. | Stereoselective synthesis of 1, 2-cis-glycofuranosides using glycofuranosyl fluorides | |
| EP0356154A2 (en) | Trehalose derivatives | |
| US4730058A (en) | Sialosylceramides and production method thereof | |
| HU196818B (en) | Process for producing syalinic acid derivatives | |
| JPH0525152A (en) | Production of 3-dpa-lactone | |
| NO148109B (en) | PROCEDURE FOR THE PREPARATION OF 5`DEOXY-5-FLUORIDINE | |
| KR950002835B1 (en) | Un-natural ceramide related compound and preparation thereof | |
| US4751290A (en) | Sialosylcerebrosides | |
| Izumi et al. | A facile synthesis of 5-thio-L-fucose and 5-thio-D-arabinose from D-arabinose | |
| Gouéth et al. | Synthesis of novel bis (glycosyl) ethers as bolaamphiphile surfactants | |
| EP3377507B1 (en) | New 5-azido-5-deoxy-2:3-isopropylidene-d-arabinose compounds; their method of manufacture and their use for the synthesis of ara-n3, kdo-n3 and 4ekdo-n3 | |
| Bravo et al. | Synthesis of erythro and threo furanoid glycals from 1-and 2-phenylselenenyl–carbohydrate derivatives | |
| JP4950521B2 (en) | Trehalose derivatives and process for producing the same | |
| EP1471071A1 (en) | Production method of 5'-acyloxynucleoside compound | |
| DD261165A5 (en) | A NEW METHOD FOR THE PRODUCTION OF SPHINGOSINE DERIVATIVES | |
| JPH0692349B2 (en) | A new method for producing optically active unsaturated amino alcohol derivatives. | |
| US4284763A (en) | Sugar acetals, their preparation and use | |
| Just et al. | Oxidation products of arachidonic acid. IV. Model studies on the attachaient of the C (13)—C (20) side-chain in the synthesis of tetrahydrofurans and pyrans 1, 2, and 3 | |
| JP2629852B2 (en) | Method for producing glycosyl compound | |
| Kudelsk | Synthesis of C-glycosides from S-glycosyl phosphorothioates | |
| Gonçalves et al. | Regioselective synthesis of long-chain ethers and their sulfates derived from methyl β-d-galactopyranoside and derivatives via dibutylstannylene acetal intermediates | |
| JP2018534313A (en) | Method for preparing 6-azido-2,4-diacetamide-2,4,6-trideoxy-D-mannose | |
| EP0540279A1 (en) | Process for preparing sugar esters | |
| Andreassen et al. | A new chemical synthesis of Ascopyrone P from 1, 5-anhydro-d-fructose |